Artificial Intelligence-Assisted Cancer Status Detection in Radiology Reports.

Cancer research is dependent on accurate and relevant information of patient's medical journey. Data in radiology reports are of extreme value but lack consistent structure for direct use in analytics. At Memorial Sloan Kettering Cancer Center (MSKCC), the radiology reports are curated using gold-standard approach of using human annotators. However, the manual process of curating large volume of retrospective data slows the pace of cancer research. Manual curation process is sensitive to volume of reports, number of data elements and nature of reports and demand appropriate skillset. In this work, we explore state of the art methods in artificial intelligence (AI) and implement end-to-end pipeline for fast and accurate annotation of radiology reports. Language models (LM) are trained using curated data by approaching curation as multiclass or multilabel classification problem. The classification tasks are to predict multiple imaging scan sites, presence of cancer and cancer status from the reports. The trained natural language processing (NLP) model classifiers achieve high weighted F1 score and accuracy. We propose and demonstrate the use of these models to assist in the manual curation process which results in higher accuracy and F1 score with lesser time and cost, thus improving efforts of cancer research. SIGNIFICANCE: Extraction of structured data in radiology for cancer research with manual process is laborious. Using AI for extraction of data elements is achieved using NLP models' assistance is faster and more accurate.

Cost-effectiveness analysis of a multiplex lateral flow rapid diagnostic test for acute non-malarial febrile illness in rural Cambodia and Bangladesh.

Background: Multiplex lateral flow rapid diagnostic tests (LF-RDTs) may aid management of patients with acute non-malarial febrile illness (NMFI) in rural south and southeast Asia. We aimed to evaluate the cost-effectiveness in Cambodia and Bangladesh of a putative, as-yet-undeveloped LF-RDT capable of diagnosing enteric fever and dengue, as well as measuring C-reactive protein (CRP) to guide antibiotic prescription, in primary care patients with acute NMFI. Methods: A country-specific decision tree model-based cost-effectiveness analysis was conducted from a health system plus limited societal perspective considering the cost of antimicrobial resistance. Parameters were based on data from a large observational study on the regional epidemiology of acute febrile illness, published studies, and procurement price lists. Costs were expressed in US$ (value in 2022), and cost-effectiveness evaluated by comparing incremental cost-effectiveness ratios with conservative opportunity cost-based willingness-to-pay thresholds and the more widely used threshold of per capita gross domestic product (GDP). Findings: Compared to standard of care, LF-RDT-augmented clinical assessment was dominant in Cambodia, being more effective and cost-saving. The cost per disability-adjusted life year (DALY) averted in Bangladesh was US$482, slightly above the conservative opportunity cost-based willingness-to-pay threshold of US$388 and considerably lower than the GDP-based threshold of US$2687. The intervention remained dominant in Cambodia and well below the GDP-based threshold in Bangladesh when antimicrobial resistance costs were disregarded. Interpretation: These findings provide guidance for academic, industry, and policymaker stakeholders involved in acute NMFI diagnostics. While definitive conclusions cannot be made in the absence of established thresholds, our results suggest that similar results are highly likely in some target settings and possible in others. Funding: Wellcome Trust, UK Government, Royal Australasian College of Physicians, and Rotary Foundation.

Phase 1 Healthy Volunteer Study of AL01211, an Oral, Non-brain Penetrant Glucosylceramide Synthase Inhibitor, to Treat Fabry Disease and Type 1 Gaucher Disease.

Glycosphingolipid (GSL) storage diseases are caused by deficiencies in the enzymes that metabolize different GSLs in the lysosome. Glucosylceramide synthase (GCS) inhibitors reduce GSL production and have potential to treat multiple GSL storage diseases. AL01211 is a potent, oral GCS inhibitor being developed for the treatment of Type 1 Gaucher disease and Fabry disease. AL01211 has minimal central nervous system penetration, allowing for treatment of peripheral organs without risking CNS-associated adverse effects. AL01211 was evaluated in a Phase 1 healthy volunteer study with single ascending dose (SAD) and multiple ascending dose (MAD) arms, to determine safety, pharmacokinetics including food effect, and pharmacodynamic effects on associated GSLs. In the SAD arm, AL01211 showed a Tmax of approximately 3.5 hours, mean clearance (CL/F) of 130.1 L/h, and t1/2 of 39.3 hours. Consuming a high-fat meal prior to dose administration reduced exposures 3.5-5.5-fold, indicating a food effect. In the MAD arm, AL01211 had an approximately 2-fold accumulation, reaching steady-state levels by 10 days. Increasing exposure inversely correlated with a decrease in GSL with plasma glucosylceramide and globotriacylceramide reduction from baseline levels, reaching 78% and 52% by day 14, respectively. AL01211 was generally well-tolerated with no AL01211 associated serious adverse events, thus supporting its further clinical development.

Enhancing microbiologically influenced corrosion protection of carbon steels with silanized epoxy-biocide hybrid coatings.

Microbial biofilms and microbiologically influenced corrosion (MIC) pose serious problems in pipelines transporting freshwater from the reservoir to service water systems and fire water systems of power reactors. The present work aims to design a silane-based epoxy-biocide hybrid coating along with antibacterial compounds on carbon steels (CS) for controlling the MIC of pipeline materials. The optimal inhibitory concentrations of biocides are identified and a robust protocol has been developed to prepare epoxy-based coatings impregnated with three biocides (25 ppm each of benzalkonium chloride, bronopol, and isothiazoline). Microbiological and accelerated corrosion studies were carried out by exposing the coated CS specimens to the enriched freshwater bacterial culture (FWC). As compared to the impedance value of 102 Ohms for the polished CS, the values were 106 and 105 Ohms, respectively, for epoxy-coated specimens (CSE) and epoxy-coated specimens impregnated with biocides (CSEB). The corrosion protection efficiency of CSE and CSEB coated specimens exposed to FWC was 99.9% and 98.1%, respectively. Confocal microscopic analysis showed the average biomass thickness was 51.3 ± 0.6 µm and 24.4 ± 0.5 µm, respectively, for CSE and CSEB specimens in comparison to 94.1 ± 0.2 µm on CS specimens. The improved anticorrosion and antifouling behaviors observed in the CSEB specimens suggest that the new coating strategy has the potential for the development of multifunctional hybrid epoxy coatings for pipeline materials to mitigate MIC-related issues in water-transporting pipeline systems.

A comprehensive review on anticorrosive/antifouling superhydrophobic coatings: Fabrication, assessment, applications, challenges and future perspectives.

Superhydrophobicity (SHP) is an incredible phenomenon of extreme water repellency of surfaces ubiquitous in nature (E.g. lotus leaves, butterfly wings, taro leaves, mosquito eyes, water-strider legs, etc). Historically, surface exhibiting water contact angle (WCA) > 150° and contact angle hysteresis <10° is considered as SHP. The SHP surfaces garnered considerable attention in recent years due to their applications in anti-corrosion, anti-fouling, self-cleaning, oil-water separation, viscous drag reduction, anti-icing, etc. As corrosion and marine biofouling are global problems, there has been focused efforts in combating these issues using innovative environmentally friendly coatings designs taking cues from natural SHP surfaces. Over the last two decades, though significant progress has been made on the fabrication of various SHP surfaces, the practical adaptation of these surfaces for various applications is hampered, mainly because of the high cost, non-scalability, lack of simplicity, non-adaptability for a wide range of substrates, poor mechanical robustness and chemical inertness. Despite the extensive research, the exact mechanism of corrosion/anti-fouling of such coatings also remains elusive. The current focus of research in recent years has been on the development of facile, eco-friendly, cost-effective, mechanically robust chemically inert, and scalable methods to prepare durable SHP coating on a variety of surfaces. Although there are some general reviews on SHP surfaces, there is no comprehensive review focusing on SHP on metallic and alloy surfaces with corrosion-resistant and antifouling properties. This review is aimed at filling this gap. This review provides a pedagogical description with the necessary background, key concepts, genesis, classical models of superhydrophobicity, rational design of SHP, coatings characterization, testing approaches, mechanisms, and novel fabrication approaches currently being explored for anticorrosion and antifouling, both from a fundamental and practical perspective. The review also provides a summary of important experimental studies with key findings, and detailed descriptions of the evaluation of surface morphologies, chemical properties, mechanical, chemical, corrosion, and antifouling properties. The recent developments in the fabrication of SHP -Cr-Mo steel, Ti, and Al are presented, along with the latest understanding of the mechanism of anticorrosion and antifouling properties of the coating also discussed. In addition, different promising applications of SHP surfaces in diverse disciplines are discussed. The last part of the review highlights the challenges and future directions. The review is an ideal material for researchers practicing in the field of coatings and also serves as an excellent reference for freshers who intend to begin research on this topic.

A nudge over the relaxation plateau: effect of pH, particle concentration, and medium viscosity on the AC induction heating efficiency of biocompatible chitosan-coated Fe3O4nanoparticles.

The effects of pH, MNP concentration, and medium viscosity on the magnetic fluid hyperthermia (MFH) properties of chitosan-coated superparamagnetic Fe3O4nanoparticles (MNPs) are probed here. Due to the protonation of the amide groups, the MNPs are colloidally stable at lower pH (∼2), but form aggregates at higher pH (∼8). The increased aggregate size at higher pH causes the Brownian relaxation time (τB) to increase, leading to a decrease in specific absorption rate (SAR). For colloidal conditions ensuring Brownian-dominated relaxation dynamics, an increase in MNP concentrations or medium viscosity is found to increase theτB. SAR decreases with increasing MNP concentration, whereas it exhibits a non-monotonic variation with increasing medium viscosity. Dynamic hysteresis loop-based calculations are found to be in agreement with the experimental results. The findings provide a greater understanding of the variation of SAR with the colloidal properties and show the importance of relaxation dynamics on MFH efficiency, where variations in the frequency-relaxation time product across the relaxation plateau cause significant variations in SAR. Further, thein vitrocytotoxicity studies show good bio-compatibility of the chitosan-coated Fe3O4MNPs. Higher SAR at acidic pH for bio-medically acceptable field parameters makes the bio-compatible chitosan-coated Fe3O4MNPs suitable for MFH applications.

Microbiologically influenced corrosion of AISI 202 and 316L stainless steels under manganese-oxidizing biofilms.

In this work, we study the microbiologically influenced corrosion (MIC) of AISI 316L (1-2% Mn) and AISI 202 (8-12% Mn) in the presence of manganese-oxidizing biofilms. Microbiological and 16S rRNA amplicon sequencing analysis on biofilms formed on the surfaces of both the SS materials after exposure to seawater for two months showed the presence of predominant Mn-oxidizing bacteria (MnOB) groups. The Mn contents in the biofilms formed on AISI 202 and 316L were 0.577 and 0.193 ppm, respectively. Mixed biofilms of 11 pure axenic cultures of MnOB isolated and identified from both the SS biofilms were used for MIC studies on SS. Electrochemical studies showed four orders of magnitude high icorr values (1.271 × 10-4 A.cm-2) and the onset of crevice corrosion potentials (502 mV) confirming the localized corrosion of AISI 202 and 316L, respectively, under MnOB biofilms. X-ray photoelectron spectroscopic (XPS) analysis on biotic surfaces showed a reduced Mn content from 10.1 to 7.9 atom.% confirming the Mn oxidation in AISI 202. This study confirms that MnOB biofilms on the SS surfaces can lead to MIC due to biogenic Mn oxidation, depletion of Fe and Mn content, and enrichment of Cr content. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03845-z.

ΔNp63 is regulated by insulin/IGF-1 signaling in normal basal/progenitor mammary cells and in luminal-type breast cancer cells.

Breast cancers are a heterogeneous group of tumors classified according to their histological growth patterns and receptor expression characteristics. Intratumor heterogeneity also exists, with subpopulations of cells with different phenotypes found in individual cancers, including cells with stem or progenitor cell properties. At least two types of breast cancer stem cells (CSCs) exist, the epithelial and the basal/mesenchymal subtypes, although how these phenotypes are controlled is unknown. ΔNp63 is a basal cell marker and regulator of stem/progenitor cell activities in the normal mammary gland and is expressed in the basal-like CSC subpopulation in some estrogen receptor-positive (ER+) and/or human epidermal growth factor receptor 2-positive (HER2+) breast adenocarcinomas. Whilst p63 is known to directly impart CSC properties in luminal breast cancer cells, how p63 is regulated and induced in these cells is unknown. We initially confirmed the existence of a small subpopulation of ΔNp63+ cells in lymph node metastases of ER+ human ductal adenocarcinomas, indicating together with previous reports that ΔNp63+ tumor cells are present in approximately 40% of these metastases. Notably, ΔNp63+ cells show a preferential location at the edge of tumor areas, suggesting possible regulation of ΔNp63 by the tumor microenvironment. Subsequently, we showed that the high levels of ΔNp63 in basal non-transformed MCF-10A mammary epithelial cells rely on insulin in their culture medium, whilst ΔNp63 levels are increased in MCF-7 ER+ luminal-type breast cancer cells treated with insulin or insulin-like growth factor 1 (IGF-1). Mechanistically, small molecule inhibitors and siRNA gene knockdown demonstrated that induction of ΔNp63 by IGF-1 requires PI3K, ERK1/2, and p38 MAPK activation, and acts through FOXO transcriptional inactivation. We also show that metformin inhibits ΔNp63 induction. These data reveal an IGF-mediated mechanism to control basal-type breast CSCs, with therapeutic implications to modify intratumor breast cancer cell heterogeneity and plasticity.

Oral ulceration (Part 1).

Ulceration is probably the oral mucosal condition seen most frequently by general dental practitioners. It is almost always painful and therefore sufferers are prompt to seek advice. An important exception to this generalisation is the occurrence of oral squamous cell carcinoma, which is often painless in its early stages. Definitive diagnosis, which requires mucosal biopsy, is mandatory for any persistent area of oral ulceration.

Oral ulceration (Part 2).

Ulceration is probably the oral mucosal condition seen most frequently by general dental practitioners. It is almost always painful and therefore sufferers are prompt to seek advice. An important exception to this generalisation is the occurrence of oral squamous cell carcinoma, which is often painless in its early stages. Definitive diagnosis, which requires mucosal biopsy, is mandatory for any persistent area of oral ulceration.

Digital pathology operations at a tertiary cancer center: Infrastructure requirements and operational cost.

Whole slide imaging is revolutionizing the field of pathology and is currently being used for clinical, educational, and research initiatives by an increasing number of institutions. Pathology departments have distinct needs for digital pathology systems, yet the cost of digital workflows is cited as a major barrier for widespread adoption by many organizations. Memorial Sloan Kettering Cancer Center (MSK) is an early adopter of whole slide imaging with incremental investments in resources that started more than 15 years ago. This experience and the large-scale scan operations led to the identification of required framework components of digital pathology operations. The cost of these components for the 2021 digital pathology operations at MSK were studied and calculated to enable an understanding of the operation and benchmark the accompanying costs. This paper describes the unique infrastructure cost and the costs associated with the digital pathology clinical operation use cases in a large, tertiary cancer center. These calculations can serve as a blueprint for other institutions to provide the necessary concepts and offer insights towards the financial requirements for digital pathology adoption by other institutions.

Barriers to Antiretroviral Medication Adherence in People Living with HIV (PLHIV) at the Time of the COVID-19 Pandemic in the Philippines.

Background: During the COVID-19 pandemic, the HIV crisis in the Philippines worsened and triggered a chain reaction that disrupted the provision and utilization of HIV services. This study aims to fill in the gap in knowledge by exploring the possible association between sociodemographic characteristics and the barriers to ART adherence for PLHIV in the Philippines at the time of the COVID-19 pandemic. Methods: A cross-sectional study was performed by using a survey questionnaire, which was distributed via online social media (Twitter). Data were analyzed using the Stata software. Results: There is a significant association between the following treatment barriers and sociodemographic characteristics: the location of treatment hubs and respondents who finished college/graduate studies; checkpoints and crossing borders; and (1) respondents from Northern Luzon Region, (2) unemployed respondents and financial assistance-1. respondents 18 to 25 years old; 2. unemployed respondents-(3) respondents who finished elementary/high school and psychosocial support-(1) respondents from the NCR; (2) respondents 26 to 30 years old, stocks of ARVs and other medicines, and employed respondents. Conclusions: The results suggest a necessity for innovative approaches to make HIV care services, particularly ART, more accessible to PLHIV during the COVID-19 pandemic. Future large-scale studies exploring the association between sociodemographic characteristics and barriers to medication adherence of PLHIV during the COVID-19 pandemic are recommended.

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry.

The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as many chemists, fully aware of the synthetic and analytical challenges, tend to modify lead compounds in a way that reduces the number of chiral centers and hence limits the potential chemical space of synthetic ligands. We have previously shown that increasing molecular complexity by introducing additional chiral centers ultimately leads to more selective and potent dopamine reuptake inhibitors. Herein, we significantly extend our structure-activity relationship of dopamine transporter-selective ligands and further demonstrate how stereoisomers of defined absolute configuration may fine-tune and direct the activity towards distinct targets. From the pool of active compounds, using the examples of stereoisomers 7h and 8h, we further showcase how in vitro activity significantly differs in in vivo drug efficacy experiments, calling for proper validation of individual stereoisomers in animal studies. Furthermore, by generating a large library of compounds with defined absolute configurations, we lay the groundwork for computational chemists to further optimize and rationally design specific monoamine transporter reuptake inhibitors.

Perspective on clinical high-risk for psychosis in Africa.

Clinical High Risk for Psychosis has evolved in recent years as a conceptual and clinical entity, representing a shift in focus from the syndromal psychosis state to a recognition of the pre-psychotic state as a period of potential preventive intervention. Much existing evidence has been generated from well-resourced countries, with a more limited body of literature available from Africa and other Majority World countries. Against a backdrop of prevailing systemic challenges, it is necessary to appraise the state of knowledge on Clinical High Risk for Psychosis in Africa. In this perspective article, we cover epidemiology, risk factors, predictors of psychosis conversion, as well as an overview of sociocultural factors, notably stigma, and the barriers to mental health services in African settings. We discuss existing and promising assessment approaches and reflect on preventive and early intervention strategies. We conclude with recommendations including the need for more clinical, longitudinal, and collaborative research anchored in an integrative transdisciplinary approach. We highlight the need for more culturally valid assessment tools and strategies to improve access to and utilization of services while also reducing stigma.

Evaluating the utility of brightfield image data for mechanism of action prediction.

Fluorescence staining techniques, such as Cell Painting, together with fluorescence microscopy have proven invaluable for visualizing and quantifying the effects that drugs and other perturbations have on cultured cells. However, fluorescence microscopy is expensive, time-consuming, labor-intensive, and the stains applied can be cytotoxic, interfering with the activity under study. The simplest form of microscopy, brightfield microscopy, lacks these downsides, but the images produced have low contrast and the cellular compartments are difficult to discern. Nevertheless, by harnessing deep learning, these brightfield images may still be sufficient for various predictive purposes. In this study, we compared the predictive performance of models trained on fluorescence images to those trained on brightfield images for predicting the mechanism of action (MoA) of different drugs. We also extracted CellProfiler features from the fluorescence images and used them to benchmark the performance. Overall, we found comparable and largely correlated predictive performance for the two imaging modalities. This is promising for future studies of MoAs in time-lapse experiments for which using fluorescence images is problematic. Explorations based on explainable AI techniques also provided valuable insights regarding compounds that were better predicted by one modality over the other.

Introducing a group-based psychoeducation intervention for older people in an inpatient mental healthcare setting.

This article reports on a service evaluation of a group-based psychoeducation programme for older people in an inpatient mental healthcare setting. It sought to explore how the programme was experienced by patients and staff, as well as its acceptability and the feasibility for implementation in the longer term. Via questionnaires, views were gathered from patients and staff. A focus group interview with staff facilitating the group sessions was also undertaken, and patient attendance records for sessions were collected and compared with demographic data relating to the two wards housed in the unit where the programme took place. The programme was generally viewed as a positive addition to care delivery by staff and patient respondents in offering an adjunct to pharmacological treatment, increasing familiarity with psychology staff, encouraging patients to develop a greater degree of mastery regarding their health and fostering mutual support among the patient community. The role of the ward environment in supporting access to group-based intervention is also considered.

Automated full body tumor segmentation in DOTATATE PET/CT for neuroendocrine cancer patients.

PURPOSE: Neuroendocrine tumors (NETs) are a rare form of cancer that can occur anywhere in the body and commonly metastasizes. The large variance in location and aggressiveness of the tumors makes it a difficult cancer to treat. Assessments of the whole-body tumor burden in a patient image allow for better tracking of disease progression and inform better treatment decisions. Currently, radiologists rely on qualitative assessments of this metric since manual segmentation is unfeasible within a typical busy clinical workflow. METHODS: We address these challenges by extending the application of the nnU-net pipeline to produce automatic NET segmentation models. We utilize the ideal imaging type of 68Ga-DOTATATE PET/CT to produce segmentation masks from which to calculate total tumor burden metrics. We provide a human-level baseline for the task and perform ablation experiments of model inputs, architectures, and loss functions. RESULTS: Our dataset is comprised of 915 PET/CT scans and is divided into a held-out test set (87 cases) and 5 training subsets to perform cross-validation. The proposed models achieve test Dice scores of 0.644, on par with our inter-annotator Dice score on a subset 6 patients of 0.682. If we apply our modified Dice score to the predictions, the test performance reaches a score of 0.80. CONCLUSION: In this paper, we demonstrate the ability to automatically generate accurate NET segmentation masks given PET images through supervised learning. We publish the model for extended use and to support the treatment planning of this rare cancer.

Targeting shared molecular etiologies to accelerate drug development for rare diseases.

Rare diseases affect over 400 million people worldwide and less than 5% of rare diseases have an approved treatment. Fortunately, the number of underlying disease etiologies is far less than the number of diseases, because many rare diseases share a common molecular etiology. Moreover, many of these shared molecular etiologies are therapeutically actionable. Grouping rare disease patients for clinical trials based on the underlying molecular etiology, rather than the traditional, symptom-based definition of disease, has the potential to greatly increase the number of patients gaining access to clinical trials. Basket clinical trials based on a shared molecular drug target have become common in the field of oncology and have been accepted by regulatory agencies as a basis for drug approvals. Implementation of basket clinical trials in the field of rare diseases is seen by multiple stakeholders-patients, researchers, clinicians, industry, regulators, and funders-as a solution to accelerate the identification of new therapies and address patient's unmet needs.