Insights from a multiscale framework on metabolic rate variation driving glioblastoma multiforme growth and invasion.

Non-physiological levels of oxygen and nutrients within the tumors result in heterogeneous cell populations that exhibit distinct necrotic, hypoxic, and proliferative zones. Among these zonal cellular properties, metabolic rates strongly affect the overall growth and invasion of tumors. Here, we report on a hybrid discrete-continuum (HDC) mathematical framework that uses metabolic data from a biomimetic two-dimensional (2D) in-vitro cancer model to predict three-dimensional (3D) behaviour of in-vitro human glioblastoma (hGB).

Comprehensive Management of Mandibular Canine Transmigration: A Multidisciplinary Approach.

Transmigration of mandibular canine teeth is a rare dental anomaly characterized by the tooth's aberrant migration through the alveolar bone. This deviation from the expected eruption pathway can lead to tooth impaction, root resorption, periodontal problems, and aesthetic concerns. The exact cause of transmigration is not fully understood, but it is believed to be influenced by a combination of genetic, developmental, and environmental factors.

A Minimal PBPK Model Describes the Differential Disposition of Silica Nanoparticles In Vivo.

Nanoparticles (NPs) have emerged as promising candidates for drug delivery due to their tunable physical and chemical properties. Among these, silica nanoparticles (SiNPs) are particularly valued for their biocompatibility and adaptability in applications like drug delivery and medical imaging. However, predicting SiNP biodistribution and clearance remains a significant challenge.

Gradient-induced instability in tumour spheroids unveils the impact of microenvironmental nutrient changes.

Tumours often display invasive behaviours that induce fingering, branching and fragmentation processes. The phenomenon, known as diffusional instability, is driven by differential cell proliferation, migration, and death due to the presence of metabolite and catabolite concentration gradients. An understanding of the intricate dynamics of this spatially heterogeneous process plays a key role in the investigation of tumour growth and invasion.

Hybridizing mechanistic modeling and deep learning for personalized survival prediction after immune checkpoint inhibitor immunotherapy.

We present a study where predictive mechanistic modeling is combined with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) immunotherapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models of key mechanisms underlying ICI therapy that may not be directly measurable in the clinic and easily measurable quantities or patient characteristics that are not always readily incorporated into predictive mechanistic models. A deep learning time-to-event predictive model trained on a hybrid mechanistic + clinical data set from 93 patients achieved higher per-patient predictive accuracy based on event-time concordance, Brier score, and negative binomial log-likelihood-based criteria than when trained on only mechanistic model-derived values or only clinical data.

Clinical Review: The Approach to the Evaluation and Management of Bilateral Adrenal Masses.

Objective: This white paper provides practical guidance for clinicians encountering bilateral adrenal masses.

Methods: A case-based approach to the evaluation and management of bilateral adrenal masses. Specific clinical scenarios presented here include cases of bilateral adrenal adenomas, hemorrhage, pheochromocytomas, metastatic disease, myelolipomas, as well as primary bilateral macronodular adrenal hyperplasia.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Background: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

Distinct Localization, Transcriptional Profiles, and Functionality in Early Life Tonsil Regulatory T Cells.

CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development, but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. In this study, we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age-related differences in Treg biology.

High LDL Particle and APOB Concentrations in Patients With Adrenal Cortical Adenomas.

Context: Patients with nonfunctioning adenomas (NFAs), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk.

Objective: This work aimed to determine the extent of lipoprotein abnormalities in NFA, MACS, and CS.

Methods: We conducted a single-center, cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142), and referent individuals (n = 202) between January 2015 and July 2022.

Iontophoresis-coupled rapidly dissolving polymeric microneedle patch of naloxone for its enhanced transdermal delivery.

The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone.

Effects of pelletization on biomethane production from wheat straw.

The high lignin content and low bulk density of wheat straw pose challenges for biogas production. To overcome these hurdles, pretreatment and biomass pelletization have emerged as viable options. Thus, this research aims to reduce the recalcitrant nature of WS by employing various thermal pretreatment techniques and identifying the optimum parameters (temperature and time).

MONAI Label: A framework for AI-assisted interactive labeling of 3D medical images.

The lack of annotated datasets is a major bottleneck for training new task-specific supervised machine learning models, considering that manual annotation is extremely expensive and time-consuming. To address this problem, we present MONAI Label, a free and open-source framework that facilitates the development of applications based on artificial intelligence (AI) models that aim at reducing the time required to annotate radiology datasets. Through MONAI Label, researchers can develop AI annotation applications focusing on their domain of expertise.

HFIP-mediated C-3-alkylation of indoles and synthesis of indolo[2,3-]quinolines & related natural products.

An expeditious metal free C-3 alkylation of indoles and its NIS-mediated deviation to indolo[2,3-]quinolines is reported. This protocol, executed in aqueous HFIP has broad substrate scope and is well inclined towards the ideas of sustainable chemistry. Applications of these strategies in accessing bioactive natural products like vibrindole, norcryptotakeine, neocryptolepine and indenoindolone scaffolds has also been demonstrated.

Hybridizing mechanistic mathematical modeling with deep learning methods to predict individual cancer patient survival after immune checkpoint inhibitor therapy.

We present a study where predictive mechanistic modeling is used in combination with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) therapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models (but may not be directly measurable in the clinic) and easily measurable quantities or characteristics (that are not always readily incorporated into predictive mechanistic models). The mechanistic model we have applied here can predict tumor response from CT or MRI imaging based on key mechanisms underlying checkpoint inhibitor therapy, and in the present work, its parameters were combined with readily-available clinical measures from 93 patients into a hybrid training set for a deep learning time-to-event predictive model.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. We developed a multiscale mechanistic model, calibrated with data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Context: Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality.

Objective: We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine.

Methods: We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802).

Prevalence and risk factors of postpartum depression in sub-Himalayan region.

Background: Postpartum depression (PPD) is a common problem faced by women after childbirth. The adverse effects of PPD upon the maternal-infant relationship and child development reinforce the need for early identification and effective treatment models. This study intends to add to the existing knowledge about the prevalence of PPD and its associated risk factors in the hilly region in Himachal Pradesh.

Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell lines .

IL-15 has shown preclinical activity by enhancing the functional maturation of natural killer (NK) cells. Clinical evaluation of the potential anticancer activity of most cytokines, including IL-15, has been limited by low tolerability and rapid clearance. Efbalropendekin Alfa (XmAb24306) is a soluble IL15/IL15-receptor alpha heterodimer complex fused to a half-life extended Fc domain (IL15/IL15Rα-Fc), engineered with mutations to reduce IL-15 affinity for CD122.