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Biomacromolecules Jul 2024Different from conventional synthetic polymers, polypeptides exhibit a distinguishing characteristic of adopting specific secondary structures, including random coils,...
Different from conventional synthetic polymers, polypeptides exhibit a distinguishing characteristic of adopting specific secondary structures, including random coils, α-helixes, and β-sheets. The conformation determines the rigidity and solubility of polypeptide chains, which further direct the self-assembly and morphology of the nanostructures. We studied the effect of distinct secondary structures on the self-assembly behavior of polytyrosine (PTyr)-derived amphiphilic copolymers. Two block copolymers of enantiopure poly(ethylene glycol)--poly(l-tyrosine) (PEG--P(l-Tyr)) and racemic poly(ethylene glycol)--poly(dl-tyrosine) (PEG--P(dl-Tyr)) were synthesized through the ring-opening polymerization of l-tyrosine -thiocarboxyanhydride (l-Tyr-NTA) and dl-tyrosine -thiocarboxyanhydride (dl-Tyr-NTA), respectively, by using poly(ethylene glycol) amine as the initiator. PEG--P(l-Tyr) adopts a β-sheet conformation and self-assembles into rectangular nanosheets in aqueous solutions, while PEG--P(dl-Tyr) is primarily in a random coil conformation with a tiny content of β-sheet structures, which self-assembles into sheaf-like nanofibrils. A pH increase results in the ionization of phenolic hydroxyl groups, which decreases the β-sheet content and increases the random coil content of the PTyr segments. Accordingly, PEG--P(l-Tyr) and PEG--P(dl-Tyr) self-assemble to form slender nanobelts and twisted nanoribbons, respectively, in alkaline aqueous solutions. The secondary structure-driven self-assembly of PTyr-derived copolymers is promising to construct filamentous nanostructures, which have potential for applications in controlled drug release.
PubMed: 38950188
DOI: 10.1021/acs.biomac.4c00437 -
Journal of Managed Care & Specialty... Jul 2024Oncology clinical trial enrollment is strongly recommended for patients with cancer who are not eligible for established and approved therapies. Many trials are specific...
Real-world clinical and economic outcomes for patients with advanced non-small cell lung cancer enrolled in a clinical trial following comprehensive genomic profiling via liquid biopsy.
BACKGROUND
Oncology clinical trial enrollment is strongly recommended for patients with cancer who are not eligible for established and approved therapies. Many trials are specific to biomarker-targeted therapies, which are typically managed as specialty pharmacy services. Comprehensive genomic profiling (CGP) of advanced cancers has been shown to detect biomarkers, guide targeted treatment, improve outcomes, and result in the clinical trial enrollment of patients, which is modeled to offset pharmacy costs experienced by US payers, yet payer policy coverage remains inconsistent. A common concern limiting coverage of CGP by payers is the potential of identifying biomarkers beyond guideline-recommended treatments, which creates a perception that insurance companies are being positioned to "pay for research." However, these biomarkers can increase clinical trial eligibility, and specialty pharmacy management may have an interest in maximizing the clinical trial enrollment of members.
OBJECTIVE
To investigate if clinical trial enrollment following liquid biopsy CGP for non-small cell lung cancer (NSCLC) is clinically and/or economically impactful from a payer claims perspective.
METHODS
Clinical and economic outcomes were studied using a real-world clinical genomic database (including payer claims data) from patients with NSCLC who enrolled in clinical trials immediately following liquid biopsy CGP (using Guardant360) and matched NSCLC patient controls also tested with liquid biopsy CGP.
RESULTS
Real-world overall survival was significantly (log-rank < 0.0001) better for patients enrolled in clinical trials with similar costs of care, albeit with more outpatient encounters among those enrolled compared with matched controls.
CONCLUSIONS
The results, together with previous analyses, suggest that, in addition to the clinical benefits associated with targeted therapies directed by CGP and other testing approaches, payers and specialty pharmacy managers may consider clinical trial direction and enrollment as a clinical and economic benefit of liquid biopsy CGP and adopt this into coverage decision frameworks and formularies.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Liquid Biopsy; Female; Male; Middle Aged; Aged; Clinical Trials as Topic; Biomarkers, Tumor; Genomics; United States
PubMed: 38950156
DOI: 10.18553/jmcp.2024.30.7.660 -
Circulation Jul 2024Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic... (Review)
Review
Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.
Topics: Humans; Apolipoproteins B; Cholesterol, LDL; Practice Guidelines as Topic; Cardiovascular Diseases; Biomarkers; Atherosclerosis; Apolipoprotein B-100
PubMed: 38950110
DOI: 10.1161/CIRCULATIONAHA.124.068885 -
Oral Diseases Jul 2024To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of... (Review)
Review
OBJECTIVES
To describe the epidemiological status of oral cancer (OC) in India along with updates on risk factors, advances and gaps in preventive measures, treatment, costs of care and monitoring.
METHODS
Two national estimates of incidence and mortality were cited, one for 2016 by the Global Burden of Disease India Study and one based on projections for 2020 by GLOBOCAN. The National Cancer Registry Project provided local and regional incidence and trends using data from 2012-2016. Scientific literature, reports of the NCRP, the IARC and government press releases were also consulted.
RESULTS
Tobacco and areca nut habits are the major risk factors for OC in India. In the 1980s, intervention studies on oral screening, awareness generation and habit cessation in rural areas reduced tobacco use and oral leukoplakia. Lately, adoption of the tobacco control law and mass media communications have resulted in decreased tobacco use. However, the increasing popularity of highly carcinogenic tobacco products containing areca nut, with evasion of their bans, is increasing OC incidence.
CONCLUSION
Despite advances in care, there is growing incidence of OC, persisting poor awareness about the need to quit tobacco/areca nut/alcohol use and go for screening. Major efforts are needed to implement preventive activities.
PubMed: 38950053
DOI: 10.1111/odi.14974 -
PLOS Digital Health Jul 2024The integration of Artificial Intelligence (AI) into public health has the potential to transform the field, influencing healthcare at the population level. AI can aid...
The integration of Artificial Intelligence (AI) into public health has the potential to transform the field, influencing healthcare at the population level. AI can aid in disease surveillance, diagnosis, and treatment decisions, impacting how healthcare professionals deliver care. However, it raises critical questions about inputs, values, and biases that must be addressed to ensure its effectiveness. This article investigates the factors influencing the values guiding AI technology and the potential consequences for public health. It outlines four key considerations that should shape discussions regarding the role of AI in the future of public health. These include the potential omission of vital factors due to incomplete data inputs, the challenge of balancing trade-offs in public health decisions, managing conflicting inputs between public health objectives and community preferences, and the importance of acknowledging the values and biases embedded in AI systems, which could influence public health policy-making.
PubMed: 38950051
DOI: 10.1371/journal.pdig.0000540 -
Pharmeuropa Bio & Scientific Notes 2024The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by...
Determination of procoagulant activity in human normal immunoglobulin preparations for therapeutic use by FXIa chromogenic assay: Evaluation of test kit sensitivity, reference standard performance and product formulation effects on the FXIa assay.
The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by the European Pharmacopoeia (Ph. Eur.) that requires 2 control reference reagents. The World Health Organization (WHO) positive control International Reference Reagent (IRR; 02/228) with a nominal titre of 8 defines the highest acceptable titre, while the negative control preparation (02/226) has a nominal titre of <2. Working reference preparations (04/132 and 04/140) were subsequently established as Biological Reference Preparations (BRPs) for the Ph. Eur., and for distribution by the United States Food and Drug Administration (US FDA) and the National Institute for Biological Standards and Control (NIBSC). Due to diminishing stocks of these working reference preparations across the 3 institutions, a joint international study was organised to establish harmonised replacement batches. Sixteen laboratories contributed data to the study to evaluate positive and negative candidate replacement batches (13/148 and 12/300, respectively) against the WHO positive and negative control IRRs and the current working reference preparations (BRPs). The results show that the candidate reference preparations (13/148 and 12/300) are indistinguishable from the corresponding IRRs and current BRPs. The candidate preparations 13/148 and 12/300 were adopted by the Ph. Eur. Commission as Immunoglobulin (anti-D antibodies test) BRP batch 2 and Immunoglobulin (anti-D antibodies test negative control) BRP batch 2 with nominal haemagglutination titres of 8 and <2, respectively. The same materials were also adopted as NIBSC and US FDA reference preparations, thus ensuring full harmonisation.
Topics: Humans; Reference Standards; Immunoglobulins, Intravenous; Rho(D) Immune Globulin; Chemistry, Pharmaceutical
PubMed: 38949845
DOI: No ID Found -
Nephrology Nursing Journal : Journal of... 2024In nephrology nursing, effective leadership ensures optimal patient care and cohesive teamwork. Despite this, nurses often overlook their leadership potential, leading...
In nephrology nursing, effective leadership ensures optimal patient care and cohesive teamwork. Despite this, nurses often overlook their leadership potential, leading to underrepresentation in health care leadership roles. This article explores the significance of nursing leadership in nephrology care and delves into the principles of transformational leadership as a fitting approach. Transformational leadership emphasizes inspiring and motivating teams toward shared goals, fostering innovation, and individualized consideration. Each aspect of transformational leadership is discussed, including how it can be applied to nephrology nursing leaders, emphasizing their role in shaping organizational culture, promoting home modalities, and fostering professional development. By embracing transformational leadership, nephrology nursing can enhance patient outcomes, address workforce challenges, and cultivate a new generation of influential leaders. This article advocates for adopting transformational leadership to meet the evolving needs of nephrology care and supporting the professional growth of nephrology nurses in leadership roles.
Topics: Leadership; Nephrology Nursing; Humans
PubMed: 38949797
DOI: No ID Found -
Medical Physics Jul 2024Lung cancer is the most common type of cancer. Detection of lung cancer at an early stage can reduce mortality rates. Pulmonary nodules may represent early cancer and...
BACKGROUND
Lung cancer is the most common type of cancer. Detection of lung cancer at an early stage can reduce mortality rates. Pulmonary nodules may represent early cancer and can be identified through computed tomography (CT) scans. Malignant risk can be estimated based on attributes like size, shape, location, and density.
PURPOSE
Deep learning algorithms have achieved remarkable advancements in this domain compared to traditional machine learning methods. Nevertheless, many existing anchor-based deep learning algorithms exhibit sensitivity to predefined anchor-box configurations, necessitating manual adjustments to obtain optimal outcomes. Conversely, current anchor-free deep learning-based nodule detection methods normally adopt fixed-size nodule models like cubes or spheres.
METHODS
To address these technical challenges, we propose a multiscale 3D anchor-free deep learning network (M3N) for pulmonary nodule detection, leveraging adjustable nodule modeling (ANM). Within this framework, ANM empowers the representation of target objects in an anisotropic manner, with a novel point selection strategy (PSS) devised to accelerate the learning process of anisotropic representation. We further incorporate a composite loss function that combines the conventional L2 loss and cosine similarity loss, facilitating M3N to learn nodules' intensity distribution in three dimensions.
RESULTS
Experiment results show that the M3N achieves 90.6% competitive performance metrics (CPM) with seven predefined false positives per scan on the LUNA 16 dataset. This performance appears to exceed that of other state-of-the-art deep learning-based networks reported in their respective publications. Individual test results also demonstrate that M3N excels in providing more accurate, adaptive bounding boxes surrounding the contours of target nodules.
CONCLUSIONS
The newly developed nodule detection system reduces reliance on prior knowledge, such as the general size of objects in the dataset, thus it should enhance overall robustness and versatility. Distinct from traditional nodule modeling techniques, the ANM approach aligns more closely with the morphological characteristics of nodules. Time consumption and detection results demonstrate promising efficiency and accuracy which should be validated in clinical settings.
PubMed: 38949577
DOI: 10.1002/mp.17283 -
Physiotherapy Theory and Practice Jul 2024Therapeutic relationship and social support are critical components in physiotherapy that shape patient outcomes. However, defining these constructs, discerning their...
BACKGROUND/PURPOSE
Therapeutic relationship and social support are critical components in physiotherapy that shape patient outcomes. However, defining these constructs, discerning their similarities and differences, and measuring them pose challenges. This article aims to facilitate scientific and clinical advancement on social support and the therapeutic relationship in physiotherapy by (a) providing conceptual clarity, (b) discussing measurement tools, and (c) offering practical recommendations for the deliberate incorporation of these constructs in clinical practice.
METHODS
This is a perspective paper drawing on examples from existing research.
KEY RESULTS
Assessing the nature and strength of social support and promoting naturally occurring social support networks are practical ways for physiotherapists to foster social support in physiotherapy clinical practice. Physiotherapists can offer direct support, facilitate the development of an individual's social skills, and promote participation in group activities. To strengthen the therapeutic relationship, it is important to maintain good communication, foster connectedness with the patient, demonstrate professional skills, and adopt a reflective practice. Physiotherapists are encouraged to establish clear roles and responsibilities, prioritize individualized patient-centered care, and involve patients in shared decision-making, ensuring congruence in goals and expectations. Willingness to dedicate time and energy within and beyond direct patient-therapist interactions can foster connections. Moreover, using the body - which is the main point of contact with patients - and physical touch can help physiotherapists to connect with patients. Finally, physiotherapists must be prepared to address and mend any conflicts which can impact the relationship's trajectory.
CONCLUSION
Social support and therapeutic relationships are complementary aspects of one's health care, and it is crucial to purposefully account for both in physiotherapy practice to optimize person-centered care and rehabilitation outcomes.
PubMed: 38949505
DOI: 10.1080/09593985.2024.2372687 -
African Journal of Primary Health Care... Jun 2024Workplace-based assessment has become increasingly crucial in the postgraduate training of specialists in South Africa, particularly for family physicians. The...
Workplace-based assessment has become increasingly crucial in the postgraduate training of specialists in South Africa, particularly for family physicians. The development of a Portfolio of Learning (PoL) has been a central focus within the discipline of family medicine for over a decade. Initially, a paper-based portfolio was adopted to collect evidence of learning for 50 out of 85 agreed exit-level outcomes. Stellenbosch University led the conversion of this portfolio into an electronic format, known as e-PoL, utilising Scorion software. The e-PoL was successfully implemented in the Western and Eastern Cape regions and was subsequently adopted nationally under the coordination of the South African Academy of Family Physicians. In 2023, the e-PoL underwent a redesign to gather evidence of learning for 22 entrustable professional activities (EPAs). Key insights from this development process underscore the importance of the PoL in supporting assessment-for-learning rather than merely assessment-of-learning. This necessitates features for feedback and interaction, ensuring that the PoL functions beyond a mere repository of forms. Additionally, the e-PoL should facilitate triangulation, aggregation, and saturation of data points to effectively measure EPAs. Furthermore, the PoL has not only documented learning but has also played a pivotal role in guiding the development of clinical training by explicitly outlining expectations for both registrars and supervisors. While the initial design and development costs are significant, operational costs become affordable when shared across all training programmes.
Topics: South Africa; Humans; Family Practice; Education, Medical, Graduate; Educational Measurement; Clinical Competence; Learning
PubMed: 38949444
DOI: 10.4102/phcfm.v16i1.4525