Efficacy and Safety of Switching to Daily Bictegravir Plus Lenacapavir From a Complex Human Immunodeficiency Virus Treatment Regimen: A Randomized, Open-Label, Multicenter Phase 2 Study (ARTISTRY-1).

Background: Complex antiretroviral therapy (ART) regimens, such as those requiring multiple tablets, several doses per day, or both, can negatively affect quality of life and treatment adherence among people with human immunodeficiency virus (HIV).

Methods: ARTISTRY-1 is a phase 2/3, operationally seamless, randomized, open-label, multicenter, active-controlled study (GS-US-621-6289; NCT05502341). Phase 2 of the study enrolled adults with plasma HIV-1 RNA <50 copies/mL receiving a complex ART regimen for ≥6 months.

Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV-1 and end-stage kidney disease on chronic haemodialysis.

Introduction: Treatment for people with HIV-1 and end-stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose-adjusted regimens, with limited data on the use of a single-tablet regimen in this population. Our aim was to assess the efficacy and safety of once-daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV-1 and ESKD on HD.

Methods: We performed an open-label extension (OLE) of an open-label, multicentre, single-group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV-1 with virological suppression.

A Multimodal Drug-Diet-Immunotherapy Combination Restrains Melanoma Progression and Metastasis.

The genetic landscape of cancer cells can lead to specific metabolic dependencies for tumor growth. Dietary interventions represent an attractive strategy to restrict the availability of key nutrients to tumors. In this study, we identified that growth of a subset of melanoma was severely restricted by a rationally designed combination therapy of a stearoyl-CoA desaturase (SCD) inhibitor with an isocaloric low-oleic acid diet.

Leveraging Artificial Intelligence for Synergies in Drug Discovery: From Computers to Clinics.

Over the period of the preceding decade, artificial intelligence (AI) has proved an outstanding performance in entire dimensions of science including pharmaceutical sciences. AI uses the concept of machine learning (ML), deep learning (DL), and neural networks (NNs) approaches for novel algorithm and hypothesis development by training the machines in multiple ways. AI-based drug development from molecule identification to clinical approval tremendously reduces the cost of development and the time over conventional methods.

A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas.

Purpose: High-grade gliomas (HGG) carry a poor prognosis, with glioblastoma accounting for almost 50% of primary brain malignancies in the elderly. Unfortunately, despite the use of multiple treatment modalities, the prognosis remains poor in this population. Our preclinical studies suggest that the presence of aromatase expression, encoded by CYP19A1, is significantly upregulated in HGGs.

Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression.

Background & Aims: Selgantolimod (GS-9688) is a Toll-like receptor 8 (TLR8) agonist that suppresses HBV in vitro. In a phase II study, we evaluated the safety and efficacy of weekly selgantolimod treatment in virally suppressed individuals with chronic HBV taking oral antiviral treatment.

Methods: Forty-eight patients were randomized into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative [n = 24 each]) to receive oral selgantolimod 3 mg, 1.

High pre-pregnancy body mass index and gestational weight gain among women belonging to upper SES from Delhi, India.

Background And Objective: With increase in prevalence of obesity and an increasing trend in the birth of macrosomic infants, Institute of Medicine (IOM) guidelines pertaining to optimal gestational weight gain (GWG) required for positive pregnancy outcome were revised in 1990 and 2009. Since, in the Indian scenario, no recommendations exist for optimum GWG for obese (OB) and overweight (OW) women, we assessed the pattern of GWG w.r.

A study of the pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed pregnant women with HIV.

Objective: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy.

Design: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1.

Methods: Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum.

Retinopathy of Prematurity: Incidence and Risk Factor Analysis in Small for Gestational Age Neonates Compared to Appropriate for Gestational Age.

Objective: To analyze the incidence of retinopathy of prematurity (ROP) among preterm neonates who were born small for gestational age (SGA) and appropriate for gestational age (AGA).

Materials And Methods: A prospective cohort study among preterm neonates born <34 weeks of gestational age (GA) and <2000 grams birth weight (BW) was conducted. The neonates were divided into AGA and SGA group.

Choroidal Thickness in Patients with Unilateral Amblyopia and Comparison between Anisometropic and Strabismic Amblyopia: A Prospective Cross-Sectional Study.

Aims And Objectives: To determine the choroidal thickness (mainly subfoveal) using spectral domain optical coherence tomography (SD-OCT) in amblyopic eyes and to compare it with the choroidal thickness (CT) of healthy fellow eyes.

Materials And Methods: In this prospective study, 140 eyes of 70 patients (aged 5-40 years) with strabismic and anisometropic amblyopia were examined using enhanced depth imaging (EDI) mode in SD-OCT. The CT was measured directly below the fovea and six other locations: 500 μ, 1000 μ, and 1500 μ from fovea in both nasal and temporal quadrants.

Calcification Detection in Intravascular Ultrasound (IVUS) Images Using Transfer Learning Based MultiSVM model.

Cardiovascular disease serves as the leading cause of death worldwide. Calcification detection is considered an important factor in cardiovascular diseases. Currently, medical practitioners visually inspect the presence of calcification using intravascular ultrasound (IVUS) images.

CADNet: an advanced architecture for automatic detection of coronary artery calcification and shadow border in intravascular ultrasound (IVUS) images.

Intravascular Ultrasound (IVUS) is a medical imaging modality widely used for the detection and treatment of coronary heart disease. The detection of vascular structures is extremely important for accurate treatment procedures. Manual detection of lumen and calcification is very time-consuming and requires technical experience.

A State-Of-The-Art Review on Coronary Artery Border Segmentation Algorithms for Intravascular Ultrasound (IVUS) Images.

Intravascular Ultrasound images (IVUS) is a useful guide for medical practitioners to identify the vascular status of coronary arteries in human beings. IVUS is a unique intracoronary imaging modality that is used as an adjunct to angioplasty to view vessel structures using a catheter with high resolutions. Segmentation of IVUS images has always remained a challenging task due to various impediments, for example, similar tissue components, vessel structures, and artifacts imposed during the acquisition process.

Refractive Error Profile of Preterm Infants at 1-Year Follow-up in a Tertiary Care Hospital.

Purpose: To study the refractive outcome in preterm infants with and without retinopathy of prematurity (ROP) in a tertiary care hospital in North India.

Methods: This prospective study was conducted on 300 consecutive premature infants with a birth weight of 2 kg or less and a gestational age of 34 weeks or less at birth. The infants were divided into three groups (no ROP, spontaneously regressed ROP, and laser-treated ROP) and were followed up at 1 year of age to assess the presence and type of refractive error in each group.

Increasing postpartum IUCD coverage through a QI initiative: a step towards reducing the unmet need of postpartum contraception.

Background: Unintended pregnancies have a negative impact on the health and economy of a nation, which can be prevented by effective family planning (FP) services. Postpartum intrauterine device (PPIUCD) is a safe and effective FP method which allows women to obtain long-acting contraception before discharge from the point of delivery. We observed poor coverage of deliveries with PPIUCD at our facility.

Gender-based differences in brain and plasma pharmacokinetics of letrozole in sprague-dawley rats: Application of physiologically-based pharmacokinetic modeling to gain quantitative insights.

Based on the discovery that the estrogen synthase aromatase (CYP19A1) is abundantly expressed in high- grade gliomas, the aromatase inhibitor, letrozole is being investigated in pre-clinical models as a novel agent against this malignancy. Here, we investigated the systemic and brain pharmacokinetics of letrozole following single and steady state dosing in both male and female Sprague-Dawley rats. Furthermore, we employed physiologically-based pharmacokinetic (PBPK) modeling to gain quantitative insights into the blood-brain barrier penetration of this drug.

Safety, Pharmacokinetics, and Pharmacodynamics of the Oral TLR8 Agonist Selgantolimod in Chronic Hepatitis B.

Background And Aims: In patients with chronic hepatitis B (CHB) infection, activation of toll-like receptor 8 may induce antiviral immunity and drive functional cure. Selgantolimod, a toll-like receptor 8 agonist, was evaluated in patients with CHB who were virally suppressed on oral antiviral treatment or viremic and not on oral antiviral treatment.

Approach And Results: In this phase 1b study, patients were randomized 4:1 to receive either selgantolimod or placebo once weekly.

Mechanisms of stearoyl CoA desaturase inhibitor sensitivity and acquired resistance in cancer.

The lipogenic enzyme stearoyl CoA desaturase (SCD) plays a key role in tumor lipid metabolism and membrane architecture. SCD is often up-regulated and a therapeutic target in cancer. Here, we report the unexpected finding that median expression of SCD is low in glioblastoma relative to normal brain due to hypermethylation and unintentional monoallelic co-deletion with phosphatase and tensin homolog (PTEN) in a subset of patients.

Sternoclavicular tuberculosis: an atypical imitator of refractory shoulder pain.

Introduction: Sternoclavicular joint tuberculosis is rare and has been presented in literature with few sporadic case reports or small case series. Rarity of the condition, nonspecific symptoms, difficulty to visualise the area on X-rays, and minimal clinical signs make diagnosis of sternoclavicular tuberculosis extremely difficult. Delay in diagnosis is therefore the common feature of all presented reports in literature.

Gestational Weight Gain among Healthy Pregnant Women from Asia in Comparison with Institute of Medicine (IOM) Guidelines-2009: A Systematic Review.

In 1990, Institute of Medicine (IOM) recommended gestational weight gain (GWG) ranges for women in the United States primarily to improve infant birth weight. Changes in key aspects of reproductive health of women of child bearing age, a rising prevalence of obesity, and noncommunicable diseases prompted the revision of IOM guidelines in 2009. However, there is no such recommendation available for Asian women.

Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD-scid gamma mice and sprague dawley rats.

Purpose: The aromatase inhibitor, letrozole, is being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs). To facilitate optimal dosing for such studies, we evaluated the plasma and brain pharmacokinetics (PK) of letrozole in NOD-scid gamma (NSG) mice, which are frequently employed for assessing efficacy against patient-derived tumor cells. Furthermore, we evaluated the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague-Dawley rats.