Implementing vision transformer for classifying 2D biomedical images.

In recent years, the growth spurt of medical imaging data has led to the development of various machine learning algorithms for various healthcare applications. The MedMNISTv2 dataset, a comprehensive benchmark for 2D biomedical image classification, encompasses diverse medical imaging modalities such as Fundus Camera, Breast Ultrasound, Colon Pathology, Blood Cell Microscope etc. Highly accurate classifications performed on these datasets is crucial for identification of various diseases and determining the course of treatment. This research paper presents a comprehensive analysis of four subsets within the MedMNISTv2 dataset: BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST. Each of these selected datasets is of diverse data modalities and comes with various sample sizes, and have been selected to analyze the efficiency of the model against diverse data modalities. The study explores the idea of assessing the Vision Transformer Model's ability to capture intricate patterns and features crucial for these medical image classification and thereby transcend the benchmark metrics substantially. The methodology includes pre-processing the input images which is followed by training the ViT-base-patch16-224 model on the mentioned datasets. The performance of the model is assessed using key metrices and by comparing the classification accuracies achieved with the benchmark accuracies. With the assistance of ViT, the new benchmarks achieved for BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST are 97.90%, 90.38%, 94.62% and 57%, respectively. The study highlights the promise of Vision transformer models in medical image analysis, preparing the way for their adoption and further exploration in healthcare applications, aiming to enhance diagnostic accuracy and assist medical professionals in clinical decision-making.

A Comparative Preclinical Evaluation of a Novel Difluprednate 0.04% BID Ophthalmic Solution and Marketed 0.05% QID Ophthalmic Emulsion.

Purpose: The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. Methods: The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. Results: In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the Cmax and AUC0-t of difluoroprednisolone 17-butyrate in humor were ∼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). Conclusions: The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.

Radiation-resistant cerium co-doped erbium-doped fibers for C- and L-band amplifiers in a high-dose gamma-radiation environment.

We experimentally demonstrate a comparative study on the radiation-resistant cerium (Ce) co-doped erbium-doped fiber amplifiers (EDFAs) exposed to a high-dose gamma-radiation environment of 1.8 kGy/h dose rate in the C and L bands. Our results show that Ce is an effective co-dopant in the aluminosilicate EDFs for suppressing radiation-induced attenuation (RIA) of more than an order of magnitude lower than the Ce-free EDF. After exposure to a high-dose gamma-radiation of up to 10 kGy, the Ce co-doped EDF still exhibits good radiation tolerance, providing 41.6 ± 2.9 dB gain and 5 ± 0.8 dB NF from 1535-1560 nm for a -25 dBm input signal. In the L-band, we report, for the first time, the radiation-resistant EDFA with the radiation-induced gain degradation (RIGD) of 3.7 dB under 2.5 kGy irradiation and 4.4 dB under 10 kGy irradiation at 1600 nm. Also, the radiation-dependent gain coefficient and gain saturation were studied in the C and L bands. A comparison of different Ce co-doped EDFs exposed to different total gamma doses reveals the radiation impact on the amplifier performance, indicating the feasibility of using Ce co-doped EDFs for space-based optical communications, requiring robust radiation stability.

Flat-gain L-band amplifier containing AlPO4 units in aluminophosphosilicate erbium-doped fibers.

We present a flat-gain single-stage L-band erbium-doped fiber amplifier (EDFA) with a gain ripple of ±0.7 dB from 1580 to 1615 nm, by using aluminophosphosilicate erbium-doped fiber (APS-EDF) with an estimated AlPO4 composition of 13.3 mol%. A series of APS-EDFs were fabricated with increasing AlPO4 and Er concentrations, while maintaining a low background loss of 0.031 ± 0.005 dB/m and preventing Er ion clustering. The spectroscopic study shows a slightly narrowing Er cross section and flattened emission cross-section spectrum in the L-band with more AlPO4, thus favoring the L-band amplification with an improved gain flatness. Also, the gain coefficient, gain saturation, and temperature-dependent gain characteristics were reported. A better temperature tolerance was observed with increasing AlPO4.

Bi-doped fiber amplifiers in the E + S band with a high gain per unit length.

We present a bismuth (Bi)-doped fiber amplifier (BDFA) operating in the 1400-1480 nm range using 35 m of Bi-doped germanosilicate fiber. A maximum gain of 23 dB for an input signal of -23dBm at 1440 nm has been achieved, which, to the best of our knowledge, is the highest gain per unit length of 0.66 dB/m reported for a BDFA. The 3 dB bandwidth is measured to be 40 nm (1415-1455 nm), and the gain coefficient is 0.2 dB/mW. A further temperature dependence study of BDFA across the temperature range of -60°C to 80°C also showed a negligible effect of temperature on the E + S band BDFA gain.

Preclinical Evaluation of a Novel Once-a-Day Brimonidine Ophthalmic Nanosuspension.

Purpose: This article aims to describe a preclinical proof of concept for a novel once-a-day (OD) brimonidine ophthalmic nanosuspension. Methods: The preclinical proof of concept was established using New Zealand white rabbits as animal models. Dose-finding, multiple-dose efficacy, ocular pharmacokinetic, and hemodynamic studies were performed in normotensive rabbits. Steroid-induced ocular hypertension model in rabbits was used to study efficacy in glaucomatous pathophysiology. The test (0.35% OD suspension) and reference (0.15% three times a day [TID] solution) were compared. Results: The intraocular pressure (IOP) reduction was sustained for 0.35% and 0.5% strengths but not for other lower strengths tested or reference strengths. A 0.35% OD suspension reduced IOP >2 mmHg after 24 h of dosing, which was not seen with the reference. After multiple dosing, 0.35% OD suspension reduced IOP by 4-6 mmHg after 24 h, which was comparable to the 0.15% TID reference solution. An ocular pharmacokinetic study showed that the brimonidine was rapidly absorbed and distributed throughout the eye after topical administration. Concentration was higher in tissues with high α2 receptors, such as cornea-conjunctiva, iris/ciliary body, and choroid/retina. The steady-state concentrations in these organs were also significant after 24 h of the last dose. There was an indication of increased plasma levels, so a hemodynamic study was performed to assess any adverse effects. All hemodynamic parameters were normal and no new unusual safety findings were observed. Conclusions: The study demonstrated that the novel brimonidine 0.35% ophthalmic nanosuspension is both safe and effective when administered OD and is comparable to the marketed reference formulation administered TID.

Uncommon Ectopic Pregnancies-Challenges in the Management.

Background: The risk factors for ectopic pregnancy are on the rise. Despite the progress (availability of serum ßhCG, USG and MRI), there are diagnostic and therapeutic challenges in the management. Up to 50% of ectopic pregnancies go undetected. Furthermore, cases seen as emergency with hemodynamic instability need urgent intervention with simultaneous arrangement of transport, blood transfusion and at times multidisciplinary team involvement. This is more challenging in a setting where resources are limited. Objective: To evaluate the outcome of women presenting with uncommon ectopic pregnancies as life-threatening emergency. Challenges encountered in diagnosis, pre-operative evaluation, decision for surgery and the procedure are presented. Patients and Methods: This is a series of twelve cases of uncommon ectopic pregnancies belonging to eight different types. These were managed under the first author during the period 2001 to 2019. Subjects were analyzed retrospectively. Results: Diagnostic dilemma was faced in majority of the cases even with the use of ultrasonography. All the conceptions were spontaneous. Emergency surgical interventions were made on the basis of clinical evaluation. Five cases presented with massive hemoperitoneum. Blood transfusion was needed in nine cases. There was no mortality. One woman (case 4), with abdominal pregnancy, went home with a live baby, after the second laparotomy. Conclusion: Uncommon ectopic pregnancies are life-threatening conditions. Clinical acumen and an alert mind are of superior value in diagnosis. Investigations are supportive. Early diagnosis and intervention are lifesaving.

Pharmacokinetics and Pharmacology of Latanoprost 0.005% without Benzalkonium Chloride Vs Latanoprost 0.005% with Benzalkonium Chloride in New Zealand White Rabbits and Beagles.

Purpose: Many intraocular pressure (IOP)-lowering medications contain benzalkonium chloride (BAK), a preservative associated with unfavorable outcomes.A formulation of latanoprost 0.005% ophthalmic without BAK is approved by the FDA and indicated for reduction of IOP in patients with open-angle glaucoma or ocular hypertension. We present two preclinical studies of latanoprost 0.005% BAK-free vs latanoprost with BAK; one examining plasma and ocular tissue pharmacokinetics (PK) in New Zealand white rabbits, and one comparing in vivo IOP-lowering efficacy in healthy beagles.Methods: In the PK study, one drop of treatment (latanoprost BAK-free or latanoprost with BAK) was instilled into both eyes of rabbits in each treatment group (n = 18). At 0.25, 0.5, 1, 4, 6, and 24 hours postdose, three rabbits per study group underwent terminal blood and tissue collection.In the IOP study, in the first dosing period, both eyes of each beagle received either 1 drop latanoprost BAK-free or latanoprost with BAK, once daily for 10 days. After a 10-day washout period, a second 10-day dosing period was conducted and latanoprost BAK-free or latanoprost with BAK were dosed in the opposite eyes, respectively. IOP measurements were taken at 1, 6, and 12 hours postdose.Results: The maximum plasma concentration for latanoprost BAK-free and latanoprost with BAK occurred 0.25 hours after administration (174.1 vs 217.2 pg/mL, respectively). Area under the concentration time curve from zero to infinity was highest in aqueous humor for latanoprost BAK-free and latanoprost with BAK (133.1 vs 119.6 hr·ng/mL, respectively) and was not estimable in vitreous humor. In beagles, once-daily administration of latanoprost BAK-free or latanoprost with BAK led to a significant reduction in IOP vs baseline (P < .001); there was no difference between groups (P > .05).Conclusions: Latanoprost BAK-free showed comparable activity in reducing IOP, and comparable plasma and ocular PK parameters to latanoprost with BAK.

Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost.

PURPOSE: Prostaglandin derivatives are used widely to reduce intraocular pressure associated with open-angle glaucoma. The most widely used prostaglandin derivative, latanoprost, is available in an ophthalmic solution that is solubilized and preserved with 0.02% benzalkonium chloride (BAK), which has been shown to be cytotoxic to corneal cells. Latanoprost ophthalmic solution with BAK requires specific storage temperatures, which can impact the supply cycle. Here, we describe the production, physicochemical characteristics, and cytotoxicity profile of a micelle formulation that solubilizes latanoprost without the need for BAK. METHODS: The optimum concentration of castor oil with the surfactant polyethylene glycol (15) hydroxystearate was determined, and the mixture stirred. Various surfactants were tested to determine the ideal mixture to form a micelle formulation. Viscosity, zeta potential, surface tension, droplet size, and osmolality of the batches were tested. The cytotoxicity of the micelle formulation was determined in a corneal cell viability assay that compared positive and negative controls, latanoprost without BAK, latanoprost with BAK, and placebo. RESULTS: A castor oil concentration of 0.15% produced a micelle formulation with a diameter of <100 nm. This micelle formulation had unique characteristics that were not mimicked when either the surfactant or the oil was changed. The physicochemical characteristics in multiple batches of the micelle formulation did not vary significantly between batches. Long-term and accelerated stability studies showed latanoprost potency remained constant for 24 months at 25°C/75% relative humidity (RH) and at 40°C/25% RH for 6 months. CONCLUSION: The micelle formulation technology system is capable of solubilizing latanoprost in an ophthalmic formulation without the need for BAK. The system is stable at room temperature.

Gain-shift induced by dopant concentration ratio in a Thulium-Bismuth doped fiber amplifier.

This paper details the effect of Thulium and Bismuth concentration ratio on gain-shift at 1800 nm and 1400 nm band in a Thulium-Bismuth Doped Fiber Amplifier (TBDFA). The effect of Thulium and Bismuth's concentration ratio on gain shifting is experimentally established and subsequently numerically modeled. The analysis is carried out via the cross relaxation and energy transfer processes between the two dopants. The energy transfer in this process was studied through experimental and numerical analysis of three samples with different Tm/Bi concentration ratio of 2, 0.5 and 0.2, respectively. The optimized length for the three samples (TBDFA-1, TBDFA-2 and TBDFA-3) was determined and set at 6.5, 4 and 5.5 m, respectively. In addition, the experimental result of Thulium Doped Fiber Amplifier (TDFA) was compared with the earlier TBDFA samples. The gain for TBDFA-1, with the highest Tm/Bi ratio, showed no shift at the 1800 nm region, while TBDFA-2 and TBDFA-3, possessing a lower Tm/Bi concentration ratio, shifted to the region of 1950 and 1960 nm, respectively. The gain shifting from 1460 nm to 1490 nm is also observed. The numerical model demonstrates that the common 3F4 layer for 1460 nm emission (3H4→3F4), and 1800 nm emission (3F4→3H6)inversely affects the 1460 nm and 1800 nm gain shifting.

Preparation and in vitro evaluation of polystyrene-coated diltiazem-resin complex by oil-in-water emulsion solvent evaporation method.

The purpose of this study was to examine the suitability of polystyrene-coated (PS-coated) microcapsules of drug-resin complex for achieving prolonged release of diltiazem-HCl, a highly water-soluble drug, in simulated gastric and intestinal fluid. The drug was bound to Indion 254, a cation-exchange resin, and the resulting resinate was microencapsulated with PS using an oil-in-water emulsion-solvent evaporation method. The effect of various formulation parameters on the characteristics of the microcapsules was studied. Mean diameter and encapsulation efficiency of the microcapsules rose with an increase in the concentration of emulsion stabilizer and the coat/core ratio, while the same characteristics tended to decrease with an increase in the volume of the organic disperse phase. The desorption of drug from the uncoated resinate was quite rapid and independent of the pH of the dissolution media. On the other hand, the drug release from the microcapsules was prolonged for different periods of time depending on the formulation parameters and was also found to be independent of the pH of the dissolution media. Both the encapsulation efficiency and the retardation of drug release were found to be dependent on the uniformity of coating, which in turn was influenced by the formulation parameters. Kinetic studies revealed that the desorption of drug from the resinate obeyed the typical particle diffusion process, whereas the drug release from the microencapsulated resinate followed the diffusion-controlled model in accordance with the Higuchi equation. PS appeared to be a suitable polymer to provide prolonged release of diltiazem independent of the pH of the dissolution media.