Role of MicroRNA-21 in Prostate Cancer Progression and Metastasis: Molecular Mechanisms to Therapeutic Targets.

The role of noncoding RNA has made remarkable progress in understanding progression, metastasis, and metastatic castration-resistant prostate cancer (mCRPC). A better understanding of the miRNAs has enhanced our knowledge of their targeting mainly at the therapy level in solid tumors, such as prostate cancer (PCa). microRNAs (miRNAs) belong to a class of endogenous RNA that deficit encoded proteins. Therefore, the role of miRNAs has been well-coined in the progression and development of PCa. miR-21 has a dual nature in its work both as a tumor suppressor and oncogenic role, but most of the recent studies showed that miR-21 is a tumor promoter and also is involved in castration-resistant prostate cancer (CRPC). Upregulation of miR-21 suppresses programmed cell death and inducing metastasis and castration resistant in PCa. miR-21 is involved in the different stages, such as proliferation, angiogenesis, migration, and invasion, and plays an important role in the progression, metastasis, and advanced stages of PCa. Recently, various studies directly linked the role of high levels of miR-21 with a poor therapeutic response in the patient of PCa. In the present review, we have explained the molecular mechanisms/pathways of miR-21 in PCa progression, metastasis, and castration resistant and summarized the role of miR-21 in diagnosis and therapeutic levels in PCa. In addition, we have spotlighted the recent therapeutic strategies for targeting different stages of PCa.

Statistical theory of fluids confined in quenched disordered porous media.

We develop a theory to calculate structural correlations and thermodynamic properties of a fluid confined in a random porous solid medium (matrix). We used density functional formalism to derive an annealed averaged expression for the density profile and excess free energy of fluid arising due to random fields of a particular realization of the matrix. After performing the second average over the quenched-disordered variables, the excess free energy is organized to give one- and two-body potentials for fluid particles. The average over disorder reduces the system to an effective one-component system of fluid in which particles feel one-body (external) potential and interact via effective pair potential. The effective pair potential is a sum of the bare (the one in the pure fluid) and the matrix-induced potential. The resulting partition function involves only fluid variables. Equations are derived for fluid-fluid and fluid-matrix correlation functions and for free energy, pressure, and chemical potential of the fluid. The theory is applied to a model system of hard spheres and results for the effective pair potential, correlation functions, and thermodynamic properties are reported. The effective pair potential is found to be attractive at the contact and develops a repulsive peak before decaying to zero. Results for pair correlation function and structure factor are compared with simulation results for several fluid densities at two matrix densities. In all the cases, a very good agreement has been found.

Impact of Plasmonic and Dielectric Substrates on the Whispering-Gallery Modes in Self-Assembled Fluorescent Semiconductor Polymer Microspheres.

In this work, the impact of metallic and dielectric conducting substrates, gold and indium tin oxide (ITO)-coated glass, on the whispering gallery modes (WGMs) of semiconductor π-conjugated polymer microspheres is investigated. Hyperspectral mapping was performed to obtain the excitation-position-dependent emission spectra of the microspheres. Substrate-dependent quenching of WGMs sensitive to mode polarization was observed and explained. On a glass substrate, both transverse-electric (TE) and transverse-magnetic (TM) WGMs are quenched due to frustrated total internal reflection. On a gold substrate, however, only the TM WGMs are allowed in symmetry to leak into surface plasmons. An atomically flat gold substrate with subwavelength slits was used to experimentally verify the leakage of WGMs into the surface plasmon polaritons (SPPs). This work provides insight into the damping mechanisms of WGMs in microspheres on metallic and dielectric substrates.

Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies.

Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient's experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-ß, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.

Diagnostic quality model (DQM): an integrated framework for the assessment of diagnostic quality when using AI/ML.

BACKGROUND: Laboratory medicine has reached the era where promises of artificial intelligence and machine learning (AI/ML) seem palpable. Currently, the primary responsibility for risk-benefit assessment in clinical practice resides with the medical director. Unfortunately, there is no tool or concept that enables diagnostic quality assessment for the various potential AI/ML applications. Specifically, we noted that an operational definition of laboratory diagnostic quality - for the specific purpose of assessing AI/ML improvements - is currently missing. METHODS: A session at the 3rd Strategic Conference of the European Federation of Laboratory Medicine in 2022 on "AI in the Laboratory of the Future" prompted an expert roundtable discussion. Here we present a conceptual diagnostic quality framework for the specific purpose of assessing AI/ML implementations. RESULTS: The presented framework is termed diagnostic quality model (DQM) and distinguishes AI/ML improvements at the test, procedure, laboratory, or healthcare ecosystem level. The operational definition illustrates the nested relationship among these levels. The model can help to define relevant objectives for implementation and how levels come together to form coherent diagnostics. The affected levels are referred to as scope and we provide a rubric to quantify AI/ML improvements while complying with existing, mandated regulatory standards. We present 4 relevant clinical scenarios including multi-modal diagnostics and compare the model to existing quality management systems. CONCLUSIONS: A diagnostic quality model is essential to navigate the complexities of clinical AI/ML implementations. The presented diagnostic quality framework can help to specify and communicate the key implications of AI/ML solutions in laboratory diagnostics.

Phytochemical Profiling and Pharmacological Evaluation of Leaf Extracts of Ruellia tuberosa L.: An In Vitro and In Silico Approach.

The present study was designed to appraise the photoprotective, antioxidant, and antibacterial bioactivities of Ruellia tuberosa leaves extracts (RtPE, RtChl, RtEA, RtAc, RtMe, and RtHMe). The results showed that, RtHMe extracts of R. tuberosa was rich in total phenolic content, i. e., 1.60 mgGAE/g dry extract, while highest total flavonoid content was found in RtAc extract, i. e., 0.40 mgQE/g. RtMe showed effective antioxidant activity (%RSA: 58.16) at the concentration of 120 µL. RtMe, RtEA and RtHMe exhibited effective in vitro antibacterial activity against Gram-negative bacteria (E. coli). In silico docking studies revealed that paucifloside (-11.743 kcal/mol), indole-3-carboxaldehyde (-7.519 kcal/mol), nuomioside (-7.275 kcal/mol), isocassifolioside (-6.992 kcal/mol) showed best docking score against PDB ID 2EX8 [penicillin binding protein 4 (dacB) from Escherichia coli, complexed with penicillin-G], PDB ID 6CQA (E. coli dihydrofolate reductase protein complexed with inhibitor AMPQD), PDB ID 2Y2I [Penicillin-binding protein 1B in complex with an alkyl boronate (ZA3)] and PDB ID 2OLV (from S. aureus), respectively. Docked phytochemicals also showed good drug likeness properties.

Metal Complexes in Cancer Treatment: Journey So Far.

Metal complexes in cancer therapy have attracted much interest mainly because metals exhibit unique characteristics, such as redox activity, metal-ligand interaction, structure and bonding, Lewis acid properties etc. In 1965, Barnett Rosenberg serendipitously discovered the metal-based compound cisplatin, an outstanding breakthrough in the history of metal-based anticancer complexes and led to a new area of anticancer drug discovery. Many metal-based compounds have been studied for their potential anticancer properties. Some of these compounds have FDA approval for clinical use, while others are now undergoing clinical trials for cancer therapy and detection. In the present study, we have highlighted the primary mode of action of metallic complexes and all FDA-approved/under clinical trial drugs with reference to cancer treatment. This review also focuses on recent progress on metal-based complexes such as platinum, ruthenium, iron, etc. with potential anticancer activities.

Electrochemical biosensors based on in situ grown carbon nanotubes on gold microelectrode array fabricated on glass substrate for glucose determination.

A highly sensitive electrochemical sensor is reported for glucose detection using carbon nanotubes grown in situ at low temperatures on photolithographically defined gold microelectrode arrays printed on a glass substrate (CNTs/Au MEA). One of the main advantages of the present design is its potential to monitor 64 samples individually for the detection of glucose. The selectivity of the fabricated MEA towards glucose detection is achieved via modification of CNTs/Au MEA by immobilizing glucose oxidase (GOx) enzyme in the matrix of poly (paraphenylenediamine) (GOx/poly (p-PDA)/CNTs/Au MEA). The electrocatalytic and electrochemical responses of the proposed sensing platform towards glucose determination were examined via cyclic voltammetry and electrochemical impedance spectroscopy. The developed impedimetric biosensor exhibits a good linear response towards glucose detection, i.e., 0.2-27.5 µM concentration range with sensitivity and detection limits of 168.03 kΩ-1 M-1 and 0.2 ± 0.0014 µM, respectively. The proposed glucose biosensor shows excellent reproducibility, good anti-interference property, and was successfully tested in blood serum samples. Further, the applicability of the proposed sensor was successfully validated through HPLC. These results supported the viability of using such devices for the simultaneous detection of multiple electroactive biomolecules of physiological relevance.

Expand and Shrink: Federated Learning with Unlabeled Data Using Clustering.

The amalgamation of the Internet of Things (IoT) and federated learning (FL) is leading the next generation of data usage due to the possibility of deep learning with data privacy preservation. The FL architecture currently assumes labeled data samples from a client for supervised classification, which is unrealistic. Most research works in the literature focus on local training, update receiving, and global model updates. However, by principle, the labeling must be performed on the client side because the data samples cannot leave the source under the FL principle. In the literature, a few works have proposed methods for unlabeled data for FL using "class-prior probabilities" or "pseudo-labeling". However, these methods make either unrealistic or uncommon assumptions, such as knowing class-prior probabilities are impractical or unavailable for each classification task and even more challenging in the IoT ecosystem. Considering these limitations, we explored the possibility of performing federated learning with unlabeled data by providing a clustering-based method of labeling the sample before training or federation. The proposed work will be suitable for every type of classification task. We performed different experiments on the client by varying the labeled data ratio, the number of clusters, and the client participation ratio. We achieved accuracy rates of 87% and 90% by using 0.01 and 0.03 of the truth labels, respectively.

Nonlinear Optical Signal Generation Mediated by a Plasmonic Azimuthally Chirped Grating.

Plasmonic gratings are simple and effective platforms for nonlinear signal generation since they provide a well-defined momentum for photon-plasmon coupling and local hot spots for frequency conversion. Here, a plasmonic azimuthally chirped grating (ACG), which provides spatially resolved broadband momentum for photon-plasmon coupling, was exploited to investigate the plasmonic enhancement effect in two nonlinear optical processes, namely two-photon photoluminescence (TPPL) and second harmonic generation (SHG). The spatial distributions of the nonlinear signals were determined experimentally by hyperspectral mapping with ultrashort pulsed excitation. The experimental spatial distributions of nonlinear signals agree very well with the analytical prediction based on photon-plasmon coupling with the momentum of the ACG, revealing the "antenna" function of the grating in plasmonic nonlinear signal generation. This work highlights the importance of the antenna effect of the gratings for nonlinear signal generation and provides insight into the enhancement mechanism of plasmonic gratings in addition to local hot spot engineering.

A histological study of the atria in patients with isolated rheumatic mitral regurgitation with and without atrial fibrillation.

BACKGROUND: There is a high incidence of atrial fibrillation (AF) in patients with isolated rheumatic mitral regurgitation (MR). The histopathologic changes in the atria of patients with isolated rheumatic MR with and without AF are unknown. OBJECTIVES: We aimed to determine the histological findings in patients with isolated severe rheumatic MR with and without AF. METHODS: Patients with severe isolated rheumatic MR undergoing valve replacement surgeries underwent endocardial biopsies from right atrial appendage, left atrial appendage, right free wall, left free wall, left posterior wall, and mitral valve. Group I consisted of patients in sinus rhythm (SR), and Group II included patients with AF. We analyzed and compared these 10 histological features in the biopsies of patients in Groups I and II. RESULTS: Of the 25 patients, 12 were in Group I and 13 in Group II. In Group I, patients had severe myocyte hypertrophy (60% vs. 18%, p = .04) that was significantly more in the right atrium (22.7% vs. 11.4%, p = .059). Interstitial adipose tissue deposition was more common in Group I (30% vs. 25%, p = .06). Interstitial fibrosis was evenly distributed at all sites without significant difference between the two groups. Group II patients had a higher prevalence and severity of vacuolar degeneration (91% vs. 60%, p = .09). CONCLUSIONS: Patients with isolated severe rheumatic MR and AF have more vacuolar degeneration in the atrial tissue. Patients with SR have myocyte hypertrophy and interstitial adipose tissue deposition. Interstitial fibrosis is uniformly distributed in patients in SR and AF.

Optical responses of Fano resonators in non-spectral parametric domains.

Fano resonance observed in various classical and quantum systems features an asymmetric spectral line shape. For designing nanoresonators for monochromatic applications, it is beneficial to describe Fano resonance in non-spectral parametric domains of critical structural parameters. We develop an analytical model of the parametric Fano profile based on a coupled harmonic oscillator model and theoretically demonstrate its application in describing the optical response of a series of waveguided plasmonic crystals of varying periodicity. The developed parametric Fano model may find applications in the design of monochromatic and spectrometer-free nanodevices.

Phenocam observed flowering anomaly of Rhododendron arboreum Sm. in Himalaya: a climate change impact perspective.

Flowering exhibits a significant relationship with environmental stimuli and changes. Effect of photoperiodism and vernalization have been well studied in flowering phenology; however, the effect of soil temperature on flowering is less explored which is one of the major factors of vegetation growth in alpine ecosystem. This study thus focuses on the effects of soil and air temperature on flowering response of Rhododendron arboreum Sm., a Himalayan tree species, which is also an indicator of spring initiation in high altitude regions. To monitor the flowering pattern, we employed automated phenocam, which was set up at 3356 masl in Tungnath (Indian Alpine region of Uttarakhand) for time-lapse photography of timberline ecotone. Soil and air temperature were recorded continuously at the timberline ecotone. Three years (2017 to 2020) of datasets were used for the present study. The phenocam observations displayed an interesting event in the year 2019-2020 with complete absence of flowering in R. arboreum population at Tungnath timberline ecotone. From the soil temperature data, an increase in winter (Dec-Jan, during which floral buds form) soil temperature, by > 1 °C, and no accumulation of freezing degree-days were found for the year 2019-2020. Air temperature however did not display any relationship with the failure of flowering, ruling out aerial chilling or frost injury of floral buds. From the results, a possible relationship between soil temperature and flowering can be suggested pointing towards necessary root apex vernalization stimulus in shallow rooted Rhododendrons. However, the dependency of flowering in Rhododendrons on winter soil temperature further requires continuous monitoring and more observations to make concrete inferences.

Adoption of E-health platforms by medical practitioners: Mediating effect of attitude on E-health platforms usage.

This study considers Theory of Reasoned Action and Technology Acceptance Model frameworks to test the mediating role of attitude towards using E-health platforms. 224 medical practitioners' responses are collected in the online mode. The mediation analysis supports the full mediation role of attitude towards using the E-health platforms in the relationship between perceived usefulness and intentions to use with (indirect effect = .15, SE = 0.03, LLCI = 0.09, and ULCI = .22). E-health platform developers should take active measures to improve the attitude of medical practitioners towards using such platforms, to derive the best results of the added features.

Signal and noise analysis for chiral structured illumination microscopy.

Recently, chiral structured illumination microscopy has been proposed to image fluorescent chiral domains at sub-wavelength resolution. Chiral structured illumination microscopy is based on the combination of structured illumination microscopy, fluorescence-detected circular dichroism, and optical chirality engineering. Since circular dichroism of natural chiral molecules is typically weak, the differential fluorescence is also weak and can be easily buried by the noise, hampering the fidelity of the reconstructed images. In this work, we systematically study the impact of the noise on the quality and resolution of chiral domain images obtained by chiral SIM. We analytically describe the signal-to-noise ratio of the reconstructed chiral SIM image in the Fourier domain and verify our theoretical calculations with numerical demonstrations. Accordingly, we discuss the feasibility of chiral SIM in different experimental scenarios and propose possible strategies to enhance the signal-to-noise ratio for samples with weak circular dichroism.

Structured illumination microscopy for simultaneous imaging of achiral and chiral domains.

We propose double structured illumination microscopy (SIM) method, which enables simultaneous imaging of achiral and chiral domains at sub-wavelength resolution. In double SIM, the illumination field is spatially structured both in the intensity and optical chirality so that moiré effects can be concurrently generated on the achiral and chiral fluorescent domains of a sample. This allows for down-modulating the high spatial frequency of both domains at the same time and thus provides sub-wavelength details after image reconstruction. We introduce the working principle of double SIM and theoretically demonstrate the feasibility of this method using different kinds of synthetic samples.

Consumer preferences for health insurance, in the wake of covid-19: Ranked features and customer segments.

The current study is conceptualized to assess the perception of the general population towards health insurance providers and the policy features, to segment them based on their attitudes. The mixed-method design is used in this study. One fifty health insurance users response were analyzed. The data analysis technique includes focus group discussion, henry garret ranking method, factor analysis and cluster analysis. This study concludes that health insurance providers needs to devise insurance policies incorporating the features of home health, telemedicine and income protection features. The existing users should be offered customization option due to covid-19 to prevent customer switch.

Anaerobic Digestion of Agri-Food Wastes for Generating Biofuels.

Presently, fossil fuels are extensively employed as major sources of energy, and their uses are considered unsustainable due to emissions of obnoxious gases on the burning of fossil fuels, which can lead to severe environmental complications, including human health. To tackle these issues, various processes are developing to waste as a feed to generate eco-friendly fuels. The biological production of fuels is considered to be more beneficial than physicochemical methods due to their environmentally friendly nature, high rate of conversion at ambient physiological conditions, and less energy-intensive. Among various biofuels, hydrogen (H2) is considered as a wonderful due to high calorific value and generate water molecule as end product on the burning. The H2 production from biowaste is demonstrated, and agri-food waste can be potentially used as a feedstock due to their high biodegradability over lignocellulosic-based biomass. Still, the H2 production is uneconomical from biowaste in fuel competing market because of low yields and increased capital and operational expenses. Anaerobic digestion is widely used for waste management and the generation of value-added products. This article is highlighting the valorization of agri-food waste to biofuels in single (H2) and two-stage bioprocesses of H2 and CH4 production.

Anomalous magnetic properties in LaFe11.5Al1.5.

We report the magnetic relaxation, DC magnetization, heat capacity, and X-ray powder diffraction studies of a melt-spun LaFe11.5Al1.5 compound executed across a temperature range of 5 to 300 K. We have found three magnetic transitions (at temperatures T1, T2, and Tord) in this compound in the zero-field cooled (ZFC) mode, and two magnetic transitions (at T2 and Tord) in the field-cooled cooling/warming (FCC/FCW) mode. The ferromagnetic transition (FM) at temperature T2 indicating hysteresis alludes to a magnetic transition of the first-order (FOT) at lower temperatures. The magnetization study reveals that meta-stable states exist in the low-temperature antiferromagnetically ordered state. Partially reversible behaviour is also observed in the 120-140 K temperature range. The heat capacity data indicates that the magnetic state of this compound is clearly different from that of spin glasses. The magnetocaloric properties of the compound are determined in the form of the isothermal magnetic entropy change (SM) and the adiabatic temperature change (ΔTad) and the utmost values of SM and Tad for a field variation of 25 kOe observed were 3.1 J kg-1 K-1 and 1.12 K respectively. The relative cooling power (RCP) is ascertained to be 216 J kg-1 for an enforced field of 25 kOe.

Kluth Type IIIb9 Variant of Esophageal Atresia.

We, herein, present an extremely rare case of an esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) with additional perforated membrane at the lower one-third of fistula. A neonate presented with difficulty in breathing and excessive frothing from the mouth. Radiograph with red rubber catheter in situ (obstruction at 10 cm from the gum margins) suggested EA with distal TEF. During thoracotomy, after ligation of fistula, a 6 Fr infant feeding tube was introduced into the distal esophagus which revealed obstruction at the lower one-third. An esophagotomy was performed; a membrane with opening at the center was identified. Following its excision, the esophageal end became dusky necessitating esophagostomy and feeding gastrostomy. A high index of suspicion for membranous obstruction at the lower one-third of fistula should be kept in mind while dealing with EA with distal TEF.