Measurable imaging-based changes in enhancement of intrahepatic cholangiocarcinoma after radiotherapy reflect physical mechanisms of response.

Background: Although escalated doses of radiation therapy (RT) for intrahepatic cholangiocarcinoma (iCCA) are associated with durable local control (LC) and prolonged survival, uncertainties persist regarding personalized RT based on biological factors. Compounding this knowledge gap, the assessment of RT response using traditional size-based criteria via computed tomography (CT) imaging correlates poorly with outcomes. We hypothesized that quantitative measures of enhancement would more accurately predict clinical outcomes than size-based assessment alone and developed a model to optimize RT. Methods: Pre-RT and post-RT CT scans of 154 patients with iCCA were analyzed retrospectively for measurements of tumor dimensions (for RECIST) and viable tumor volume using quantitative European Association for Study of Liver (qEASL) measurements. Binary classification and survival analyses were performed to evaluate the ability of qEASL to predict treatment outcomes, and mathematical modeling was performed to identify the mechanistic determinants of treatment outcomes and to predict optimal RT protocols. Results: Multivariable analysis accounting for traditional prognostic covariates revealed that percentage change in viable volume following RT was significantly associated with OS, outperforming stratification by RECIST. Binary classification identified ≥33% decrease in viable volume to optimally correspond to response to RT. The model-derived, patient-specific tumor enhancement growth rate emerged as the dominant mechanistic determinant of treatment outcome and yielded high accuracy of patient stratification (80.5%), strongly correlating with the qEASL-based classifier. Conclusion: Following RT for iCCA, changes in viable volume outperformed radiographic size-based assessment using RECIST for OS prediction. CT-derived tumor-specific mathematical parameters may help optimize RT for resistant tumors.

Polyhydroxyalkanoates Production from Cheese Whey under Near-Seawater Salinity Conditions.

Treating saline streams presents considerable challenges due to their adverse effects on conventional biological processes, thereby leading to increased expenses in managing those side streams. With this in consideration, this study explores into the potential for valorizing fermented cheese whey (CW), a by-product of the dairy industry, into polyhydroxyalkanoates (PHA) using mixed microbial cultures (MMC) under conditions of near-seawater salinity (30 gNaCl/L). The selection of a PHA-accumulating MMC was successfully achieved using a sequential batch reactor operated under a feast and famine regime, with a hydraulic retention time of 14.5hours, a variable solids retention time of 3 and 4.5 days, and an organic loading rate (OLR) of 60 Cmmol/(L d). The selected culture demonstrated efficient PHA production rates and yields, maintaining robust performance even under high salinity conditions. During PHA accumulation, a maximum PHA content in biomass of 56.4% wt. was achieved for a copolymer P(3HB-co-3HHx) with a 3HHx content of 7%. Additionally, to asses the capacity of the culture to produce polymers with different compositions, valeric acid was supplemented to the real fermented feedstock which resulted in the production of terpolymers P(3HB-co-3HV-co-3HHx) with varied monomeric content and a higher maximum PHA content of 62% wt. Additionaly, this study highlights the potential utilization of seawater as alternative to freshwater for PHA production, thereby enhancing circular economy principles and promoting environmental sustainability.

Tailoring 3D-printed sensor properties with reduced-graphene oxide: improved conductive filaments.

The development of a tailored filament is reported composed of reduced graphene oxide (rGO) and carbon black (CB) in a polylactic acid (PLA) matrix and its use in the production of electrochemical sensors. The electrodes containing rGO showed superior performance when compared with  those prepared in the absence of this material. Physicochemical and electrochemical characterizations of the electrodes showed the successful incorporation of both rGO and CB and an improved conductivity in the presence of rGO (lower resistance to charge transfer). As a proof-of-concept, the developed electrodes were applied to the detection of the forensic analytes TNT and cocaine. The electrodes containing rGO presented a superior analytical performance for both TNT and cocaine detection, showing the lower limit of detection values (0.22 and 2.1 µmol L-1, respectively) in comparison with pure CB-PLA electrodes (0.93 and 11.3 µmol L-1, respectively). Besides, better-defined redox peaks were observed, especially for TNT, as well as increased sensitivity for both molecules.

Sensitive Monitoring of the Minimum Inhibitor Concentration under Real Inorganic Scaling Scenarios.

Flow assurance is a long-term challenge for oil and gas exploration as it plays a key role in designing safe and efficient operation techniques to ensure the uninterrupted transport of reservoir fluids. In this regard, the sensitive monitoring of the scale formation process is important by providing an accurate assessment of the minimum inhibitor concentration (MIC) of antiscale products. The optimum dosage of antiscale inputs is of pivotal relevance as their application at concentrations both lower and higher than MIC can imply pipeline blockages, critically hindering the entire supply chain of oil-related inputs and products to society. Using a simple and low-cost impedimetric platform, we here address the monitoring of the scale formation on stainless-steel capillaries from its early stages under real topside (ambient pressure and 60 °C) and subsea (1000 psi and 80 °C) sceneries of the oil industry. The method could continuously gauge the scale formation with a sensitivity higher than the conventional approach, i.e., the tube blocking test (TBT), which proved to be mandatory for avoiding misleading inferences on the MIC. In fact, whereas our sensor could entail accurate MICs, as confirmed by scanning electron microscopy, TBT suffered from negative deviations, with the predicted MICs being lower than the real values. Importantly, the impedance measurements were performed through a hand-held, user-friendly workstation. In this way, our method is envisioned to deliver an attractive and readily deployable platform to combat the scale formation issues because it can continuously monitor the salt precipitation from its early stages and yield the accurate determination of MIC.

Combinatorial Wnt signaling landscape during brachiopod anteroposterior patterning.

BACKGROUND: Wnt signaling pathways play crucial roles in animal development. They establish embryonic axes, specify cell fates, and regulate tissue morphogenesis from the early embryo to organogenesis. It is becoming increasingly recognized that these distinct developmental outcomes depend upon dynamic interactions between multiple ligands, receptors, antagonists, and other pathway modulators, consolidating the view that a combinatorial "code" controls the output of Wnt signaling. However, due to the lack of comprehensive analyses of Wnt components in several animal groups, it remains unclear if specific combinations always give rise to specific outcomes, and if these combinatorial patterns are conserved throughout evolution. RESULTS: In this work, we investigate the combinatorial expression of Wnt signaling components during the axial patterning of the brachiopod Terebratalia transversa. We find that T. transversa has a conserved repertoire of ligands, receptors, and antagonists. These genes are expressed throughout embryogenesis but undergo significant upregulation during axial elongation. At this stage, Frizzled domains occupy broad regions across the body while Wnt domains are narrower and distributed in partially overlapping patches; antagonists are mostly restricted to the anterior end. Based on their combinatorial expression, we identify a series of unique transcriptional subregions along the anteroposterior axis that coincide with the different morphological subdivisions of the brachiopod larval body. When comparing these data across the animal phylogeny, we find that the expression of Frizzled genes is relatively conserved, whereas the expression of Wnt genes is more variable. CONCLUSIONS: Our results suggest that the differential activation of Wnt signaling pathways may play a role in regionalizing the anteroposterior axis of brachiopod larvae. More generally, our analyses suggest that changes in the receptor context of Wnt ligands may act as a mechanism for the evolution and diversification of the metazoan body axis.

Diagnosis and management of blunt cerebrovascular injuries: What you need to know.

ABSTRACT: Blunt cerebrovascular injuries are not as rare as they were once thought to be-but they still have the same potential for disastrous outcomes. They may occur following any trauma, but more common with higher energy transfer mechanisms. If stroke occurs, prompt recognition and treatment offers the best chance for optimal outcome. Early diagnosis and provision of antithrombotic therapy may prevent strokes, so screening of asymptomatic patients is recommended. Herein we will present what you need to know to diagnose and manage blunt cerebrovascular injury.

Lymphotoxin beta-activated LTBR/NIK/RELB axis drives proliferation in cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis and limited treatment options. Prior evidence highlighted a significant contribution of the non-canonical NF-κB signalling pathway in initiation and aggressiveness of different tumour types. Lymphotoxin-ß (LTß) stimulates the NF-κB-inducing kinase (NIK), resulting in the activation of the transcription factor RelB. However, the functional contribution of the non-canonical NF-κB signalling pathway via the LTß/NIK/RelB axis in CCA carcinogenesis and progression has not been established. METHODS: Human CCA-derived cell lines and organoids were examined to determine the expression of NF-κB pathway components upon activation or inhibition. Proliferation and cell death were analysed using real-time impedance measurement and flow cytometry. Immunoblot, qRT-PCR, RNA sequencing and in situ hybridization were employed to analyse gene and protein expression. Four in vivo models of iCCA were used to probe the activation and regulation of the non-canonical NF-κB pathway. RESULTS: Exposure to LTα1/ß2 activates the LTß/NIK/RelB axis and promotes proliferation in CCA. Inhibition of NIK with the small molecule inhibitor B022 efficiently suppresses RelB expression in patient-derived CCA organoids and nuclear co-translocation of RelB and p52 stimulated by LTα1/ß2 in CCA cell lines. In murine CCA, RelB expression is significantly increased and LTß is the predominant ligand of the non-canonical NF-κB signalling pathway. CONCLUSIONS: Our study confirms that the non-canonical NF-κB axis LTß/NIK/RelB drives cholangiocarcinogenesis and represents a candidate therapeutic target.

Imaging Guidelines during Percutaneous Liver Ablation to Optimize Outcomes and Patient Safety.

Image-guided ablation procedures have become a mainstay in cancer therapy. Typically performed from a percutaneous approach, thermal-based ablation procedures rely heavily on imaging guidance both prior to and during the procedure itself. Advances in imaging as they relate to ablation procedures are as important to successful treatments as advancements in the ablation technology itself. Imaging as it relates to procedural planning, targeting and monitoring, and assessment of procedural endpoint is the focus of this article.

Identification of A0 minimum ablative margins for colorectal liver metastases: multicentre, retrospective study using deformable CT registration and artificial intelligence-based autosegmentation.

BACKGROUND: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting. METHODS: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour or local tumour progression) rates by minimum ablative margin across all institutions and identifying an intraprocedural contrast-enhanced CT-based minimum ablative margin associated with a 3-year local disease progression rate of less than 1%. RESULTS: A total of 400 ablated colorectal liver metastases (median diameter of 1.5 cm) in 243 patients (145 men; median age of 62 [interquartile range 54-70] years) were evaluated, with a median follow-up of 26 (interquartile range 17-40) months. A total of 119 (48.9%) patients with 186 (46.5%) colorectal liver metastases were from international institutions B, C, and D that were not involved in the software development. Three-year local disease progression rates for 0 mm, >0 and <5 mm, and 5 mm or larger minimum ablative margins were 79%, 15%, and 0% respectively for institution A (where the software was developed) and 34%, 19%, and 2% respectively for institutions B, C, and D combined. Local disease progression risk decreased to less than 1% with an intraprocedurally confirmed minimum ablative margin greater than 4.6 mm. CONCLUSION: A minimum ablative margin of 5 mm or larger demonstrates optimal local oncological outcomes. It is proposed that an intraprocedural minimum ablative margin of 5 mm or larger, confirmed using biomechanical deformable image registration, serves as the A0 for colorectal liver metastasis thermal ablation.

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

First Direct Measurement of the 64.5 keV Resonance Strength in the

The CNO cycle is one of the most important nuclear energy sources in stars. At temperatures of hydrostatic H-burning (20 MK

Morphogenic Modeling of Corrosion Reveals Complex Effects of Intermetallic Particles.

Corrosion processes are often discussed as stochastic events. Here, it is shown that some of these seemingly random processes are not driven by nanoscopic fluctuations but rather by the spatial distribution of micrometer-scale heterogeneities that trigger fast reactions associated with corrosion. Using a novel excitable reaction-diffusion model, corrosion waves traveling over the metal surface and the associated material loss are described. This resulting nonuniform corrosion penetration, seen as a height loss in modeling, exposes buried intermetallic particles, which depending on the local electrochemical state of the surface trigger or block new waves. Informed by quantitative experimental data for the Mg-Al-Zn alloy AZ31B, wave speeds, wave widths, and average material loss are accurately captured. Morphogenic mitigation based on wave-breaking microparticles is also simulated. While AZ31B corrosion is identified as a process driven by rare-wave events, this study predicts several other corrosion regimes that proceed via spots or patchy patterns, opening the door for new protection, design, and prediction strategies.

Spatial and seasonal distribution of Leptospira spp. seropositive horses in the Northeast region of Brazil.

Leptospirosis is an anthropozoonosis of economic and public health importance, caused by bacteria of the genus Leptospira. Horses are deemed important in its transmission chain due to their proximity to humans, and because the species is often asymptomatic, making these animals potential silent reservoirs. In this context, the objectives of this study were to determine the prevalence of seropositive horses for Leptospira spp., and to identify the presence of Leptospira spp. serogroups and antibody titers, the occurrence of areas with higher density of infection cases and demographic characteristics associated with seropositivity in the states of Paraíba (PB), Pernambuco (PE), Rio Grande do Norte (RN) and Ceará (CE), in the Northeast region of Brazil, during rainy (May and June) and dry (October and November) seasons from 2017 to 2019. Using the microscopic agglutination test (MAT), 1152 equine serum samples from 225 municipalities were analyzed. Anti-Leptospira antibodies were detected in 23.9 % (95 % CI= 21.4 - 26.3 %) of the samples in the three-year period, with a frequency of 30.4 % (95 % CI= 26.7 - 34.2 %) during the rainy period (with greater emphasis on the Ballum serogroup) and 17.4 % (95 % CI= 14.3 - 20.5 %) in the dry period (with greater emphasis on the Sejroe serogroup). Age of horses ≥ 6 years (6-10 years, 11-15 years and ≥ 16 years), rainy season, and animal belonging to Pernambuco state were factors with higher seropositivities. Regarding spatial distribution, a higher percentage of seropositive animals was observed in Pernambuco (P < 0.05), in interstate border areas, and large urban centers, with a spatial cluster detected in the dry season of 2018 with relative risk of 2.8 (P = 0.049) times higher in municipalities within the cluster. It is suggested that measures for controlling rodents and contact with wild animals in equine farming, both in rainy and dry periods, combined with care regarding the use of pastures shared with cattle and the adoption of immunoprophylaxis are important in preventing and controlling leptospirosis in horses in the Northeast region of Brazil.

Dual-Target Additively Manufactured Electrochemical Sensor for the Multiplexed Detection of Protein A29 and DNA of Human Monkeypox Virus.

Herein, we present the first 3D-printed electrochemical portable biodevice for the detection of monkeypox virus (MKPV). The electrochemical device consists of two biosensors: an immunosensor and a genosensor specifically designed for the detection of the protein A29 and a target DNA of MKPV, respectively. The electrodes were manufactured using lab-made ultraflexible conductive filaments composed of carbon black, recycled PLA from coffee pods, and castor oil as a plasticizer. The sensors created through 3D printing technology exhibited good reproducibility and repeatability of analytical responses. Furthermore, both the immunosensor and genosensor demonstrated excellent MKPV detection capabilities, with a linear range from 0.01 to 1.0 µmol L-1 for the antigen and 0.1 to 20.0 µmol L-1 for the DNA target. The biosensors achieved limits of detection of 2.7 and 29 nmol L-1 for the immunosensor and genosensor, respectively. Interference tests conducted with the biosensors demonstrated their selectivity for MKPV. Moreover, analyses of fortified human serum samples showed recoveries close to 100%, confirming the absence of significant matrix effects for MKPV analysis. Therefore, the 3D-printed multiplex device represents a viable and highly promising alternative for on-site, portable, and rapid point-of-care MKPV monitoring.

How to Improve Sustainability in Fused Filament Fabrication (3D Printing) Research?

This review aims to provide an overview of sustainable approaches that can be incorporated into well-known procedures for the development of materials, pre- and post-treatments, modifications, and applications of 3D-printed objects, especially for fused filament fabrication (FFF). Different examples of conductive and non-conductive bespoke filaments using renewable biopolymers, bioplasticizers, and recycled materials are presented and discussed. The main final characteristics of the polymeric materials achieved according to the feedstock, preparation, extrusion, and treatments are also covered. In addition to recycling and remanufacturing, this review also explores other alternative approaches that can be adopted to enhance the sustainability of methods, aiming to produce efficient and environmentally friendly 3D printed products. Adjusting printing parameters and miniaturizing systems are also highlighted in this regard. All these recommended strategies are employed to minimize environmental damage, while also enabling the production of high-quality, economical materials and 3D printed systems. These efforts align with the principles of Green Chemistry, Sustainable Development Goals (SDGs), 3Rs (Reduce, Reuse, Recycle), and Circular Economy concepts.

Safety and Efficacy of Percutaneous Cryoablation for Recurrent or Metastatic Soft Tissue Sarcoma in Adult Patients.

Background: Treatment options are limited in patients with recurrent or metastatic disease after initial treatment of soft tissue sarcoma (STS) by surgical resection, radiation, or systemic therapy. Percutaneous cryoablation may provide a complementary minimally invasive option in this setting. Objective: To assess the safety and efficacy of percutaneous cryoablation performed for local control of treatment-refractory recurrent or metastatic STS. Methods: This single-institution retrospective study included adult patients who underwent percutaneous cryoablation from March 2016 to April 2023 to achieve local control of recurrent or metastatic STS after earlier treatment (surgery, radiation, or chemotherapy). For each treated lesion, a single interventional radiologist re-reviewed intraprocedural images to assess for adequate coverage by the ice ball of the entire lesion and a ≥5-mm margin in all dimensions. Complications and outcomes were extracted from medical records. The primary endpoint for procedure efficacy was 1-year local progression-free survival. Results: The study included 141 patients (median age, 66 years; 90 female, 51 male) who underwent 217 cryoablation procedures to treat 250 recurrent or metastatic STS lesions. The most common STS histologic types were leiomyosarcoma (56/141) and liposarcoma (39/141). Lesions had a mean long-axis diameter of 2.0 cm (range, 0.4-11.0 cm). Adequate ice-ball coverage was achieved for 82% (204/250) of lesions. The complication rate was 2% (4/217), entailing three major complications and one minor complication. Patients' median post-ablation follow-up was 25 months (range, 3-80 months). Local progression-free survival was 86% at 1 year and 79% at 2 years. Chemotherapy-free survival was 45% at 1 year and 31% at 2 years. Overall survival (OS) was 89% at 1 year and 80% at 2 years. In Kaplan-Meier analysis, leiomyosarcoma, in comparison with liposarcoma, had significantly higher local progression-free survival, but no significant difference in OS. In multivariable analysis, factors independently associated with an increased risk for local progression included inadequate ice-ball coverage (HR=7.73) and a lesion location of peritoneum (HR=3.63) or retroperitoneum (HR=3.71) relative to lung. Conclusion: Percutaneous cryoablation has a favorable safety and efficacy profile in patients with recurrent or metastatic STS after earlier treatments. Clinical Impact: Percutaneous cryoablation should be considered for local control of treatment-refractory STS.

Measurement of the Isolated Nuclear Two-Photon Decay in

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100 keV and half-lives as short as ∼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

Tale of Two Polymorphs: Investigating the Structural Differences and Dynamic Relationship between Nirmatrelvir Solid Forms (Paxlovid).

Two anhydrous polymorphs of the novel antiviral medicine nirmatrelvir were discovered during the development of Paxlovid, Pfizer's oral Covid-19 treatment. A comprehensive experimental and computational approach was necessary to distinguish the two closely related polymorphs, herein identified as Forms 1 and 4. This approach paired experimental methods, including powder X-ray diffraction and single-crystal X-ray diffraction, solid-state experimental methods, thermal analysis, solid-state nuclear magnetic resonance and Raman spectroscopy with computational investigations comprising crystal structure prediction, Gibbs free energy calculations, and molecular dynamics simulations of the polymorphic transition. Forms 1 and 4 were ultimately determined to be enantiotropically related polymorphs with Form 1 being the stable form above the transition temperature of ∼17 °C and designated as the nominated form for drug development. The work described in this paper shows the importance of using highly specialized orthogonal approaches to elucidate the subtle differences in structure and properties of similar solid-state forms. This synergistic approach allowed for unprecedented speed in bringing Paxlovid to patients in record time amidst the pandemic.

Using Patient-Specific 3D Modeling and Simulations to Optimize Microwave Ablation Therapy for Liver Cancer.

Microwave ablation (MWA) of liver tumors presents challenges like under- and over-ablation, potentially leading to inadequate tumor destruction and damage to healthy tissue. This study aims to develop personalized three-dimensional (3D) models to simulate MWA for liver tumors, incorporating patient-specific characteristics. The primary objective is to validate the predicted ablation zones compared to clinical outcomes, offering insights into MWA before therapy to facilitate accurate treatment planning. Contrast-enhanced CT images from three patients were used to create 3D models. The simulations used coupled electromagnetic wave propagation and bioheat transfer to estimate the temperature distribution, predicting tumor destruction and ablation margins. The findings indicate that prolonged ablation does not significantly improve tumor destruction once an adequate margin is achieved, although it increases tissue damage. There was a substantial overlap between the clinical ablation zones and the predicted ablation zones. For patient 1, the Dice score was 0.73, indicating high accuracy, with a sensitivity of 0.72 and a specificity of 0.76. For patient 2, the Dice score was 0.86, with a sensitivity of 0.79 and a specificity of 0.96. For patient 3, the Dice score was 0.8, with a sensitivity of 0.85 and a specificity of 0.74. Patient-specific 3D models demonstrate potential in accurately predicting ablation zones and optimizing MWA treatment strategies.

Patient Acceptability and Preferences for Solid Oral Dosage Form Drug Product Attributes: A Scoping Review.

Background: There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence adherence and, therefore, drug product effectiveness. The aim of this review was to assess current understanding of patient acceptability and preferences for solid oral dosage form (SODF) drug product attributes, and the potential impact of these attributes on patient behaviors and outcomes. Patients and Methods: A scoping review was conducted. Embase, Ovid MEDLINE®, and PubMed® were searched for full-text articles published between January 2013 and May 2023. Following screening and assessment against predefined inclusion criteria, data were analyzed thematically. Results: Nineteen studies were included. Four overarching domains of drug product attributes were identified and summarized in a framework: appearance, swallowability, palatability, and handling. Each domain was informed by specific drug product attributes: texture, form, size, shape, color, marking, taste, mouthfeel, and smell. The most frequently studied domains were swallowability and appearance, while the most studied attributes were size, shape, and texture. Smell, marking, and mouthfeel were the least studied attributes. Texture intersected all domains, while form, shape, and size intersected appearance, swallowability, and handling. Swallowability and size appeared to be the key domain and attribute, respectively, to consider when designing drug products. Few studies explored the impact of drug product attributes on behaviors and outcomes. Conclusion: While existing studies of drug product attributes have focused on appearance and swallowability, this review highlighted the importance of two less well-understood domains-palatability and handling-in understanding patients' acceptability and preferences for SODF drug products. The framework provides a tool to facilitate patient-centric design of drug products, organizing and categorizing physical drug product attributes into four overarching domains (appearance, swallowability, palatability, and handling), encouraging researchers to comprehensively assess the impact of drug product attributes on patient acceptability, preferences, and outcomes.

Medicines come in a variety of types and forms. These include tablets and capsules. Factors, such as the size and shape of tablets, can affect how people take medicines. However, patients are rarely involved in designing the medicines that they take. In this study, researchers summarized 19 studies published between 2013 and 2023. They wanted to understand how different factors, like size and shape, affect patients' preferences, ability, and willingness to take medicines. Researchers focused on the "physical" aspects of medicines and found 4 common themes: 1) what they look like (appearance), 2) how easy they are to swallow (swallowability), 3) how they taste and feel in the mouth (palatability), and 4) how easy they are to handle (handling). Eight factors were also found: color, markings, shape, size, smell, taste, texture, and how a medicine feels in the mouth (mouthfeel). Most studies focused on what medicines look like and how easy they are to swallow. The factors that researchers mostly looked at were the size, shape, and texture of medicines. The design of medicines can impact patients of different ages, though there may be specific needs for certain groups of patients, including children, older adults, and people with certain diseases. Patient input should become a part of future medicines design to ensure their acceptability.