A Comprehensive Review on the Electrocardiographic Manifestations of Cardiac Sarcoidosis: Patterns and Prognosis.

PURPOSE OF REVIEW: Cardiac sarcoidosis (CS) refers to cardiac involvement in sarcoidosis and is usually associated with worse outcomes. This comprehensive review aims to elucidate the electrocardiographic (ECG) signs and features associated with CS, as well as examine modern techniques and their importance in CS evaluation. RECENT FINDINGS: The exact pathogenesis of CS is still unclear, but it stems from an abnormal immunological response triggered by environmental factors in individuals with genetic predisposition. CS presents with non-cardiac symptoms; however, conduction system abnormalities are common in patients with CS. The most common electrocardiographic (ECG) signs include atrioventricular blocks and ventricular tachyarrhythmia. Distinct patterns, such as fragmented QRS complexes, T-wave alternans, and bundle branch blocks, are critical indicators of myocardial involvement. The application of advanced ECG techniques such as signal-averaged ECG, Holter monitoring, wavelet-transformed ECG, microvolt T-wave alternans, and artificial intelligence-supported analysis holds promising outcomes for opportune detection and monitoring of CS. Timely utilisation of inexpensive and readily available ECG possesses the potential to allow early detection and intervention for CS. The integration of artificial intelligence models into ECG analysis is a promising approach for improving the ECG diagnostic accuracy and further risk stratification of patients with CS.

A graph neural network approach for predicting drug susceptibility in the human microbiome.

Recent studies have illuminated the critical role of the human microbiome in maintaining health and influencing the pharmacological responses of drugs. Clinical trials, encompassing approximately 150 drugs, have unveiled interactions with the gastrointestinal microbiome, resulting in the conversion of these drugs into inactive metabolites. It is imperative to explore the field of pharmacomicrobiomics during the early stages of drug discovery, prior to clinical trials. To achieve this, the utilization of machine learning and deep learning models is highly desirable. In this study, we have proposed graph-based neural network models, namely GCN, GAT, and GINCOV models, utilizing the SMILES dataset of drug microbiome. Our primary objective was to classify the susceptibility of drugs to depletion by gut microbiota. Our results indicate that the GINCOV surpassed the other models, achieving impressive performance metrics, with an accuracy of 93% on the test dataset. This proposed Graph Neural Network (GNN) model offers a rapid and efficient method for screening drugs susceptible to gut microbiota depletion and also encourages the improvement of patient-specific dosage responses and formulations.

Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin's and non-Hodgkin's lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

Synergistic adsorption of methylene blue using ternary composite of phosphoric acid geopolymer, calcium alginate, and sodium lauryl sulfate.

The removal of dyes from the aquatic ecosystem is necessary being a major threat to life. For enhanced remediation of methylene blue (MB) dye, a new ternary biopolymer-geopolymer-surfactant composite adsorbent is synthesized by combining phosphoric acid geopolymer (PAGP), calcium alginate (Alg), and sodium lauryl sulfate (SLS). During the synthesis of the composites, PAGP and SLS were mixed with the alginate matrix, producing porous hybrid beads. The PAGP-SLS-alginate (PSA) beads prepared were characterized using different analytical tools, i.e., scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffractometry (XRD), surface area and porosimetery (SAP), and thermogravimetric analysis (TGA). To ascertain the ideal conditions for the adsorption process, a batch reactor procedure was used to investigate the effects of several parameters on MB adsorption, including pH (2, 4, 6, 8, 10), PSA adsorbent dosage (0.06-0.12 g), MB concentration (50-500 mg/L), contact time (15 to 300 min), and temperature (25, 35, and 45 °C). The SEM investigation indicated that ~ 1860 µm-sized PSA beads with 6-8 µm voids are generated. Based on XRD, FTIR, and SAP examinations, the material is amorphous, having numerous functional groups and an average pore size of 6.42 nm. Variation of pH has a little effect on the adsorption process, and the pH of 7.44 was found to be the pHpzc of the PSA beads. According to the findings of the batch study, equilibrium adsorption was obtained in 270-300 min, showing that the adsorption process was moderately slow-moving and effective. The dye adsorption linearly increased with initial dye concentration over concentration range of 50-500 mg/L and reciprocally decreased with rise in temperature. 0.06 g adsorbent dose, 25 °C, pH10, and 270 min were found to be the better conditions for adsorption experiments. Langmuir isotherm fitted well compared to Freundlich, Temkin, and Dubinin-Radushkevich (DR) isotherm models on the experimental data, and the maximum adsorption capacity(qmax) calculated was 1666.6 mg. g-1. Pseudo-second-order (PSO) kinetics model and multi steps (two) intra particle diffusion (IPD) model fitted well on the adsorption kinetics data. The system's entropy, Gibbs free energy, and change in enthalpy were measured and found to be -109.171 J. mol-1. K-1, - 8.198 to - 6.014 kJ. mol-1, and - 40.747 kJ. mol-1. Thermodynamics study revealed that adsorption process is exothermic, energetically favorable and resulting in the decrease in randomness. Chemisorption is found to be the dominant mechanism as confirmed by pH effect, Langmuir isotherm, PSO kinetics, IPD model, and thermodynamics parameters. PSA beads were successfully regenerated using ethanol in a course of 120 min and re-used for five times. To sum up, the PSA adsorbent's impressive adsorption capability of 1666.66 mg/g highlights its potential as a successful solution for methylene blue removal. The results of this study add to the expanding corpus of information on sophisticated adsorption materials and demonstrate PSA's potential for real-world uses in wastewater treatment and environmental clean-up.

Developing novel multifunctional protective clothes for disabled individuals using bio-based electrospun nanofibrous membranes.

A novel kind of protective apparel for handicapped persons has been created with bio-based electrospun nanofibrous (NFs) membranes. Hydrophobic membranes with fine polylactic acid (PLA) NFs had a smooth, bead-less structure with an average diameter of 950 nm. The hydrophilic layer has a similar pattern but a smaller fiber diameter dispersion and an average diameter of 750 nm. The silica nanoparticle-modified super-hydrophobic top layer (contact angle, ~153°) repels water and keeps the user dry. Super-hydrophilic silver nanoparticles in the fabric's bottom layer react with perspiration to kill microorganisms. The fabric's porosity (avg. 1.2-1.5 µm) allows for breathability, while silica nanoparticles boost infrared radiation reflection, keeping users cool on hot days. The dual-layer textile has 4.9 MPa ultimate tensile strength and 68 % elongation compared to the membrane's super-hydrophobic and super-hydrophilic layers. Wearing protective clothes reduced hand temperature by 25 % in direct sunlight and 13 % in a sun simulator with 1 Sun. This fabric will work well for adult diapers, outdoor clothing, and disability accessories. Overall, the protective textiles may improve the quality of life for disabled and elderly people by providing usable textile items adapted to their needs.

Pharmacological activation of mesenchymal stem cells increases gene expression pattern of cell adhesion molecules and fusion with neonatal cardiomyocytes.

Cellular therapy is considered a better option for the treatment of degenerative disorders. Different cell types are being used for tissue regeneration. Despite extensive research in this field, several issues remain to be addressed concerning cell transplantation. One of these issues is the survival and homing of administered cells in the injured tissue, which depends on the ability of these cells to adhere. To enhance cell adherence and survival, Rap1 GTPase was activated in mesenchymal stem cells (MSCs) as well as in cardiomyocytes (CMs) by using 8-pCPT-2'-O-Me-cAMP, and the effect on gene expression dynamics was determined through quantitative reverse transcriptase-polymerase chain reaction analysis. Pharmacological activation of MSCs and CMs resulted in the upregulation of connexin-43 and cell adhesion genes, which increased the cell adhesion ability of MSCs and CMs, and increased the fusion of MSCs with neonatal CMs. Treating stem cells with a pharmacological agent that activates Rap1a before transplantation can enhance their fusion with CMs and increase cellular regeneration.

Surface Engineering of the Mechanical Properties of Molecular Crystals via an Atomistic Model for Computing the Facet Stress Response of Solids.

Invited for the cover of this issue are Mubarak Almehairbi, Vikram C. Joshi, Changquan Calvin Sun and Sharmarke Mohamed. The image depicts the digital exploration of the mechanical properties of crystals on specific facets that may be of interest for materials applications by "dialing-in" their stress response. Read the full text of the article at 10.1002/chem.202400779.

A systematic first-principles investigation of the structural, electronic, mechanical, optical, and thermodynamic properties of Half-Heusler ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) for spintronics and optoelectronics applications.

This paper is the first to look at the structural, electronic, mechanical, optical, and thermodynamic properties of the ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) half-Heusler (HH) using DFT based first principles method. The lattice parameters that we have calculated are very similar to those obtained in prior investigations with theoretical and experimental data. The positive phonon dispersion curve confirm the dynamical stability of ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The electronic band structure and DOS confirmed that the studied materials ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) are direct band gap semiconductors. The investigation also determined significant constants, including dielectric function, absorption, conductivity, reflectivity, refractive index, and loss function. These optical observations unveiled our compounds potential utilization in various electronic and optoelectronic device applications. The elastic constants were used to fulfill the Born criteria, confirming the mechanical stability and ductility of the solids ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn). The calculated elastic modulus revealed that our studied compounds are elastically anisotropic. Moreover, ANiX (ASc, Ti, Y, Zr, Hf; XBi, Sn) has a very low minimum thermal conductivity (Kmin), and a low Debye temperature (θD), which indicating their appropriateness for utilization in thermal barrier coating (TBC) applications. The Helmholtz free energy (F), internal energy (E), entropy (S), and specific heat capacity (Cv) are determined by calculations derived from the phonon density of states.

Technical considerations in robotic aberrant right subclavian artery resection for dysphagia lusoria.

Dysphagia lusoria occurs due to compression of the esophagus as an aberrant right subclavian artery (ARSA) crosses the mediastinum. Surgical management includes open, hybrid, and endovascular techniques, with no consensus gold standard. There are few reports of robotic-assisted ARSA resection. We describe the innovative technique and outcomes for two patients who successfully underwent robotic-assisted transthoracic resection of an ARSA after right carotid-subclavian bypass for dysphagia lusoria. Both patients experienced improvement or resolution of their dysphagia and no major complications. In select patients with a noncalcified origin of the ARSA without aneurysmal degeneration, the robotic-assisted approach represents a viable option.

Bedaquiline: An Insight Into its Clinical Use in Multidrug-Resistant Pulmonary Tuberculosis.

Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.

Does ponticulus posticus affect vertebral artery diameter.

PURPOSE: Ponticulus Posticus, atlantooccipital ligament ossification-induced anomaly, surrounds the vertebral artery and the first cervical nerve root. It is believed to wrap around the first cervical nerve root and the vertebral artery, causing compression. We hypothesized that it would also reduce the diameter of the vertebral artery. METHODS: Between January 1, 2022, and December 31, 2022, cervical spine CT scans taken for any reason were retrospectively reviewed. The images of 1365 patients suitable for evaluation were evaluated by two expert radiologists in 3 dimensions. Among patients with PP, those who underwent cervical angiography were identified for vertebral artery diameter measurement. RESULTS: The average age of the 1365 individuals included in the study (732 males, 633 females) was 55.78 (± 18.85) with an age range of 1-96. Among this group, PP was detected in 288 individuals, resulting in a total prevalence of 21.1%. Right and left vertebral artery diameters were significantly lower in patients with complete PP compared to the absent group (p < 0,001, p < 0,001, respectively). Additionally, it was observed that width and height diameters and artery diameters were positively correlated in patients with Complete PP. CONCLUSIONS: Ponticulus posticus can cause vertebrobasilar insufficiency by reducing the diameter of the vertebral artery. Therefore, imaging and detailed evaluation of this region are important in symptomatic patients.

What is the state of the art on traditional medicine interventions for zoonotic diseases in the Indian subcontinent? A scoping review of the peer-reviewed evidence base.

BACKGROUND: Traditional medicine (TM) interventions are plausible therapeutic alternatives to conventional medical interventions against emerging and endemic zoonotic diseases, particularly in low-and middle-income countries that may lack resources and infrastructure. Despite the growing popularity in the usage of TM interventions, their clinical safety and effectiveness are still contested within conventional healthcare in many countries. METHODS: We conducted a scoping review of the peer-reviewed literature that synthesises and maps the evidence on TM interventions for the treatment and prevention of zoonoses on the Indian subcontinent. The region, a global hotspot of biodiversity and emerging infections, is characterised by high prevalence of TM use. Based on the scientific literature (mostly case study research, n=l06 studies), our review (1) maps the scope of the literature, (2) synthesises the evidence on the application of TM interventions for zoonoses, and (3) critically reflects on the state of TM and identifies areas for future research focus. RESULTS: The evidence synthesis confirmed widespread usage of TM interventions for zoonoses on the subcontinent, with the majority of research reported from India (n=99 studies, 93.4%), followed by Pakistan (n=3 studies, 2.8%), Bangladesh (n=2 studies, 1.9%), and Sri Lanka (n=1, 0.9%). Most of the reviewed studies reported on ethno-medicinal uses of plant species, primarily for treating dengue (n=20 studies), tuberculosis (n=18 studies), Escherichia coli infection (n=16 studies), lymphatic filariasis and cholera (n=9 apiece). However, the evidence on the safety and effectiveness of these reported TM interventions is limited, indicating that these data are rarely collected and/or shared within the peer-reviewed literature. CONCLUSION: This review thus highlights that, whilst TMs are already being used and could offer more widely accessible interventions against emerging and endemic zoonoses and ectoparasites, there is an urgent need for rigorous clinical testing and validation of the safety and effectiveness of these interventions.

Narrative cave art in Indonesia by 51,200 years ago.

Previous dating research indicated that the Indonesian island of Sulawesi is host to some of the oldest known rock art1-3. That work was based on solution uranium-series (U-series) analysis of calcite deposits overlying rock art in the limestone caves of Maros-Pangkep, South Sulawesi1-3. Here we use a novel application of this approach-laser-ablation U-series imaging-to re-date some of the earliest cave art in this karst area and to determine the age of stylistically similar motifs at other Maros-Pangkep sites. This method provides enhanced spatial accuracy, resulting in older minimum ages for previously dated art. We show that a hunting scene from Leang Bulu' Sipong 4, which was originally dated using the previous approach to a minimum of 43,900 thousand years ago (ka)3, has a minimum age of 50.2 ± 2.2 ka, and so is at least 4,040 years older than thought. Using the imaging approach, we also assign a minimum age of 53.5 ± 2.3 ka to a newly described cave art scene at Leang Karampuang. Painted at least 51,200 years ago, this narrative composition, which depicts human-like figures interacting with a pig, is now the earliest known surviving example of representational art, and visual storytelling, in the world3. Our findings show that figurative portrayals of anthropomorphic figures and animals have a deeper origin in the history of modern human (Homo sapiens) image-making than recognized to date, as does their representation in composed scenes.

Backward neural network (BNN) based multilevel control for enhancing the quality of an islanded RES DC microgrid under variable communication network.

Microgrids (MGs) and energy communities have been widely implemented, leading to the participation of multiple stakeholders in distribution networks. Insufficient information infrastructure, particularly in rural distribution networks, is leading to a growing number of operational blind areas in distribution networks. An optimization challenge is addressed in multi-feeder microgrid systems to handle load sharing and voltage management by implementing a backward neural network (BNN) as a robust control approach. The control technique consists of a neural network that optimizes the control strategy to calculate the operating directions for each distributed generating point. Neural networks improve control during communication connectivity issues to ensure the computation of operational directions. Traditional control of DC microgrids is susceptible to communication link delays. The proposed BNN technique can be expanded to encompass the entire multi-feeder network for precise load distribution and voltage management. The BNN results are achieved through mathematical analysis of different load conditions and uncertain line characteristics in a radial network of a multi-feeder microgrid, demonstrating the effectiveness of the proposed approach. The proposed BNN technique is more effective than conventional control in accurately distributing the load and regulating the feeder voltage, especially during communication failure.

Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.

Pancreatic cancer remains a significant health issue with limited treatment options. The tumor stroma, a complex environment made up of different cells and proteins, plays a crucial role in tumor growth and chemoresistance. Targeting tumor stroma, consisting of diverse non-tumor cells such as fibroblasts, extracellular matrix (ECM), immune cells, and also pre-vascular cells is encouraging for remodeling solid cancers, such as pancreatic cancer. Remodeling the stroma of pancreas tumors can be suggested as a strategy for reducing resistance to chemo/immunotherapy. Several studies have shown that phytochemicals from plants can affect the tumor environment and have anti-cancer properties. By targeting key pathways involved in stromal activation, phytochemicals may disrupt communication between the tumor and stroma and make tumor cells more sensitive to different treatments. Additionally, phytochemicals have immunomodulatory and anti-angiogenic properties, all of which contribute to their potential in treating pancreatic cancer. This review will provide a detailed look at how phytochemicals impact the tumor stroma and their effects on pancreatic tumor growth, spread, and response to treatment. It will also explore the potential of combining phytochemicals with other treatment options like chemotherapy, immunotherapy, and radiation.

Quantitative analysis of solid dosage forms of Atenolol by Raman spectroscopy.

OBJECTIVE: To develop a Raman spectroscopy-based analytical model for quantification of solid dosage forms of active pharmaceutical ingredient (API) of Atenolol.Significance: For the quantitative analysis of pharmaceutical drugs, Raman Spectroscopy is a reliable and fast detection method. As part of this study, Raman Spectroscopy is explored for the quantitative analysis of different concentrations of Atenolol. METHODS: Various solid-dosage forms of Atenolol were prepared by mixing API with excipients to form different solid-dosage formulations of Atenolol. Multivariate data analysis techniques, such as Principal Component Analysis (PCA) and Partial least square regression (PLSR) were used for the qualitative and quantitative analysis, respectively. RESULTS: As the concentration of the drug increased in formulation, the peak intensities of the distinctive Raman spectral characteristics associated with the API (Atenolol) gradually increased. Raman spectral data sets were classified using PCA due to their distinctive spectral characteristics. Additionally, a prediction model was built using PLSR analysis to assess the quantitative relationship between various API (Atenolol) concentrations and spectral features. With a goodness of fit value of 0.99, the root mean square errors of calibration (RMSEC) and prediction (RMSEP) were determined to be 1.0036 and 2.83 mg, respectively. The API content in the blind/unknown Atenolol formulation was determined as well using the PLSR model. CONCLUSIONS: Based on these results, Raman spectroscopy may be used to quickly and accurately analyze pharmaceutical samples and for their quantitative determination.

Assessment of evidence based care and uniformity of practices through implementation of standardized medical protocols and guidelines in pediatric emergency departments.

OBJECTIVE: This study aims to assess compliance with medical protocols and outcomes, as well as determine the consistency in clinical practice across different Pediatric Emergency Departments (PED) in public sector hospitals of a low-middle income country. METHODS: A retrospective analysis was conducted on patients presenting to PEDs of five public sector hospitals, namely Civil Hospital Karachi (PED 1), National Institute of Child Health (PED 2), Abbasi Shaheed Hospital (PED 3), Sheikh Zayed Hospital Larkana (PED 4), and Ghulam Muhammad Mahar College Hospital Sukkur (PED 5). The analysis covered a three-month period from February 1, 2023, to April 30, 2023. Patients diagnosed with Acute asthma, Sepsis, and Septic Shock during the study duration were included. Outcomes for each disease were evaluated based on compliance with standardized protocols.The statistical significance of data was measured by adding the p values. RESULTS: 110,450 patients visited PED during the study period and mortality rate was 2% (n=2193). 12% (13,240) were diagnosed with the three diseases during the study period. Sepsis was on top (74%, n=9,751), followed by Septic Shock (14%, n=1898), and Acute Asthma (12%, n=1591). The overall compliance rate for the three diseases was 77% (n = 10,240). Adherence to standard protocols were 98% (n = 1561) for acute asthma, 85% (n = 8240) for Sepsis, and 23% (n = 439) for Septic Shock across the five emergency departments. Of the patients who were managed according to standard protocol, 31% (n = 3135) were discharged, 30% (n- 3094) were admitted, 11% (n = 1151) were referred, 15% (n = 1501) left against medical advice and 13% (n = 1359) did not survive. On the other hand, in patients where there was noncompliance to standard protocols, 27% (n = 805) did not survive, 27% (n = 807) were discharged, 24% (n = 710) were admitted, 8% (n = 260) were referred and 14% (n = 418) left against medical advice. The differences in adherence rates among the three diseases were statistically significant (p < 0.001). CONCLUSION: The overall mortality rate was 2% in these five emergency departments and the medical protocol was followed in every third patient out of fourth in those three diseases. The survival rate till ED disposition was doubled in those patients for whom medical protocols were followed as compared to those for non-compliant. The majority of PED demonstrated good compliance with standardized practices. However, this study identified areas that require attention and further training, especially early recognition and management of septic shock where compliances seem alarmingly low. Our data analysis indicates that adherence to guidelines has resulted in uniformity in clinical practice and the provision of early evidence-based quality care. Nevertheless, there is still room for improvement in ensuring consistent adherence to medical protocols in pediatric emergency settings and thus improving patient outcomes.