Medicine Research Research Articles

Development of Proteasome Inhibitors for Cancer Therapy

Review Development of Proteasome Inhibitors for Cancer Therapy Xu Chen † , Xuan Wu † , Linyan Li, and Xiaoming Zhu * State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China * Correspondence: xmzhu@must.edu.mo Received: 12 January 2024 Accepted: 19 February 2024 Published: 18 March 2024 Abstract: The ubiquitin proteasome system (UPS) is considered a crucial degradation machinery in cellular processes of protein quality control and homeostasis. Dysregulation of the UPS is closely associated with many diseases. The proteasome is a key core component of the UPS, which can prevent the accumulation of misfolded proteins and regulate various cellular processes such as cell cycle, apoptosis, and immune responses. In the past two decades, a total of three proteasome inhibitors have been approved for the treatment of hematological malignancies, including bortezomib, carfilzomib, and ixazomib. Additionally, accumulating reports have suggested that some natural product-derived proteasome inhibitors have been developed as anti-cancer drug candidates. In this review, we summarize the development of proteasome inhibitors as well as the mechanisms involved, clinical application progress, and drug resistance. The natural products of proteasome inhibitors and their future perspectives will also be discussed.

A CRITICAL REVIEW OF KARAVELLAKA (MOMORDICA CHARANTIA LINN.) AS A VISHAGNA DRAVYA (ANTI POISONOUS DRUG)

BACKGROUND: Our ancestors know the day-to-day common and medicinal uses of Karavellaka (Momordica charantia Linn.). It is also known to be utilised by folklore practitioners for medicinal purposes. MATERIALS AND METHODS: Here is an attempt made to gather information about Karavellaka as Vishagna through the literary resources from various classical and contemporary texts and other publications like Kriyakaumudi, Indian Medicinal Plants, Rasatarangini and research updates. OBSERVATION AND RE-SULT: The reference to Vishagna property is available in the classics and is supported by research articles. CONCLUSION: Studies prove the (Vishagna) anti-poisonous activity of Karavellaka utilised either Ekamoolika Dravya or another form of Aushadhi Yoga and expanded the scope of exploration of its medicinal benefits.

Inference on the reliability of inverse Weibull with multiply Type-I censored data

Inverse Weibull (IW) distribution is widely used due to its non-monotonic hazard function. For the IW distribution, existing research on statistical inference has mostly focused on censored data, but there has been no study on multiply Type-I censoring until now as far as we know. The multiple Type-I censoring, acted as an extended form of Type-I censoring, is frequently encountered in industry and medicine research, which also needs to be paid attention. Thus, this study conducts detailed analyses on the reliability of IW distribution with multiply Type-I censored data, including point estimation and confidence interval (CI) construction. Four methods, including the maximum likelihood estimation (MLE), least square estimation (LSE), and two Bayesian estimations, namely MCMC and Lindley, are adopted in point estimation. Results show that the Lindley method performs best with small mission times, while MLE is optimal for large mission times. Specifically, for the CIs construction, we proposed a pivotal quantity based on LSE to construct the CIs of reliability and compare it with two popular methods, Fisher information matrix (FIM) derivation and MCMC algorithm. Our proposed method shows competitive performance as the MCMC and outperforms FIM. Finally, those estimation methods are applied to an example for illustration.

Underfunding for Research Training and Career Development: The Impact on Family Medicine Research.

The National Institutes of Health and related federal awards for research training (RT) and research career development (RCD) are designed to prepare applicants for research careers. We compared funding rates for RT and RCD for anesthesiology, dermatology, emergency medicine, family medicine, internal medicine, neurology, obstetrics-gynecology, pathology, pediatrics, and psychiatry. We estimated the denominator using the number of residency graduates from different specialties from 2001 to 2010 from the Association of American Medical Colleges data. For the numerator, we used published data on federally funded awards by specialty from 2011 to 2020. We also examined the correlation between RCD funding and overall research funding. Family medicine had the lowest rate per graduating resident for RT (0.01%) and RCD (0.77%) awards among 10 specialties and was lower than the mean/median for the other nine specialties, ranging from 2.15%/1.19% and 9.83%/8.74%. We found a strong correlation between rates of RCD awards and mean federal funding per active physician, which was statistically significant (ρ=0.77, P=.0098). Comparatively low rates for family medicine awards for RT and RCD plausibly contribute to poor federal funding for family medicine research, underscoring the need to bolster the research career pathway in family medicine.

After a few months, what are the uses of OpenAI’s ChatGPT in medicine? A Scopus-based systematic review

<b>Introduction:</b> Acute ChatGPT, an artificial inteeligence-powered chatbot, presents a potential influence on healthcare and research in medicine. In this investigation, we systematically reviewed medical literature regarding the utilization of ChatGPT, utilizing the Scopus database.<br /> <b>Methods: </b>This systematic review follows the preferred reporting items for systematic reviews and meta-analyses guidelines, and according to the search in Scopus, 11,219 articles were identified. Original studies, clinical trials, correspondence articles, letters, notes, and research protocols were included, resulting in 14 studies.<br /> <b>Results: </b>All studies were published in 2023, among them 35.7% (5/14) were editorials and 14.3% (2/14) were opinion or perspective articles. Only one study (19) conducted a pilot study on the application of ChatGPT in medical diagnosis. Furthermore, 64.3% of the studies were published in quartile 1 journals according to Scimago rankings, and the USA had the highest production of articles on ChatGPT in medicine (35.7%). The included studies highlighted the potential and challenges of ChatGPT in various domains of healthcare. Ethical concerns, such as data privacy and bias, were also analyzed. Various fields of health were evaluated with ChatGPT, including nuclear medicine, gynecology, nuclear medicine, and emergency medicine. ChatGPT was considered a tool to improve patient education. ChatGPT has a promising role in scientific writing, emphasizing the need for human involvement, ethical guidelines, and addressing concerns related to bias, fabrication, and plagiarism.<br /> <b>Conclusions: </b>Scopus-retrieved articles underscored the potential advantages and ethical dilemmas associated with the integration of ChatGPT in healthcare. While ChatGPT demonstrated promising applications in various medical domains, caution, further evaluation, and ethical considerations are needed for responsible implementation in real-world clinical settings.

MedChatZH: A tuning LLM for traditional Chinese medicine consultations

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers

BackgroundAccurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.MethodsEight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF.ResultsFor [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%).ConclusionsFor [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization.

Brain Organoids, the Path Forward?

Brain Organoids, the Path Forward?

Recruitment, Retention, and Training of Citizen Scientists in Translational Medicine Research: A Citizen Science Initiative on Non-Alcoholic Fatty Liver Disease.

Citizen science is a participatory science approach in which members of the public (citizens) collaborate with scientists and professional researchers and become involved in research and innovation activities, resulting in the co-creation of scientific knowledge and innovation. Citizen science has been widely applied in research, particularly in the social sciences, environmental sciences, information and communication technologies, and public health. However, the application of this approach inclinical sciences, particularly in translational medicine research, is still nascent. This exploratory study involved members of the public (citizen scientists) in a translational medicineexperiment on non-alcoholic fatty liver disease that incorporated a lifestyle and weight-loss intervention. The aim of this paper is to report successful methods and approaches for the recruitment, retention, and training of citizen scientists. For the citizen scientists' recruitment, online calls placed on the websites of our research project and biomedical research centerand targeted emails were the most helpful. Of the 14 members of the public who expressed interest in our study, six were recruited as citizen scientists. Citizen scientists were mostly female (n = 5, 83%), white (n = 3, 50%), over 50 years of age (n = 4, 67%), educated to postgraduate level (n = 5, 83%), and either retired or not in employment (n = 5, 83%). The retention rate was 83% (n = 5), and the dropout rate was 17% (n = 1). We arranged instructor-led interactive online training sessions (an hour-long one-on-one session and two-hour group sessions). Research skills training covered ethics in research and qualitative and quantitative data analysis. Citizen scientists were given several incentives, such as reimbursement of travel and care costs, selection as citizen scientists of the month, publications of their blogs and perspective articles, and co-authorship and acknowledgement in papers and project deliverables. To conclude, members of the public (particularly middle-aged white women with postgraduate education) are interested in becoming citizen scientists in translational medicine research. Their retention rate is higher, and they can contribute to different research activities. However, they need training to develop their research skills and expertise. The training should be simple, comprehensive, and flexible to accommodate the schedules of individual citizen scientists. They deserve incentives as they work on a voluntary basis.

AagingBase: a comprehensive database of anti-aging peptides.

The process of aging is an intrinsic and inevitable aspect of life that impacts every living organism. As biotechnological advancements continue to shape our understanding of medicine, peptide therapeutics have emerged as a promising strategy for anti-aging interventions. This is primarily due to their favorable attributes, such as low immunogenicity and cost-effective production. Peptide-based treatments have garnered widespread acceptance and interest in aging research, particularly in the context of age-related therapies. To effectively develop anti-aging treatments, a comprehensive understanding of the physicochemical characteristics of anti-aging peptides is essential. Factors such as amino acid composition, instability index, hydrophobic areas and other relevant properties significantly determine their efficacy as potential therapeutic agents. Consequently, the creation of 'AagingBase', a comprehensive database for anti-aging peptides, aims to facilitate research on aging by leveraging the potential of peptide therapies. AagingBase houses experimentally validated 282 anti-aging peptides collected from 54 research articles and 236 patents. Employing state-of-the-art computational techniques, the acquired sequences have undergone rigorous physicochemical calculations. Furthermore, AagingBase presents users with various informative analyses highlighting atomic compositions, secondary structure fractions, tertiary structure, amino acid compositions and frequencies. The database also offers advanced search and filtering options and similarity search, thereby aiding researchers in understanding their biological functions. Hence, the database enables efficient identification and prioritization of potential peptide candidates in geriatric medicine and holds immense potential for advancing geriatric medicine research and innovations. AagingBase can be accessed without any restriction. Database URL: https://project.iith.ac.in/cgntlab/aagingbase/.

Poly(hydroxyalkanoates): Emerging Biopolymers in Biomedical Fields and Packaging Industries for a Circular Economy

AbstractPoly(hydroxyalkanoates) (PHAs) are a class of sustainable, bio-based thermoplastic polymers with attractive physiochemical properties, including non-toxicity, biocompatibility, elastomeric behavior by design, and piezoelectric characteristics. In the ongoing effort to reduce plastics waste, PHAs can play a substantial role due to their inherent biodegradability free of microplastics, customizable properties, and versatile applications. This includes their tremendous potential in a broad range of biomedical applications. Biomass-based materials have recently gained great interest in the health sector, given the vast amount of interdisciplinary research in bioengineering and medicine. Implantable biomaterials should not elicit any negative response at the implantation site, which differentiates them from general-purpose polymers. PHAs do not induce any thrombosis or antigenic response even after being in contact with blood in the human body during long-term use. The biocompatibility of PHAs is also a key factor in the rapid growth and proliferation of tissues onto and within these materials when served as tissue engineering scaffolds. By application, the biomedical field was estimated to be the second-largest market share for PHAs, in terms of volume, in 2022. While PHA-based materials bring forth a broad range of opportunities, they also present challenges that have limited their widespread use and a greater market share. A better understanding of their physiochemical properties and biodegradation rates, production challenges, and the need for cost-effective strategies are some of the hurdles that need to be addressed. This review paper provides an overview of the commonly used PHA homopolymers and copolymers in biomedical fields and packaging industries. The introduction of the manuscript presents the concept of bioplastics and their environmental significance, highlighting the urgent need for alternatives to conventional fossil-based plastics. The next sections briefly cover the synthesis, properties, as well as homopolymer and copolymer formulations, followed by the application of PHA-based materials in the biomedical field. Current opportunities and challenges, together with some insight into the future gathered from the published studies, have been brought in the concluding section of this paper.

A Comprehensive Review on Peptic Ulcer

Abstract: Up to 10% people in the world are affected by a chronic condition known as peptic ulcer. Peptic ulcer development is influenced by the pH of gastric juice and a decline in mucosal defenses. Protonpump inhibitors, histamine (H2) receptor antagonists, prostaglandin analogues and sucralfate have all been used to treat peptic ulcer disease. There has been a continuing search for an appropriate, palliative, and curative agent for the treatment of peptic ulcer disease using natural materials of plant and animal origin due to the complexity, cost, and toxicity of these medications. The goal of this review was to examine medicinal plants, phytochemicals, pathways, and research models that have been applied to the treatment of PUD in order to assess the potential contribution of natural substances to the development of herbal treatments for PUD. A literature search was used to find information utilising electronic databases such as Web of Science, Google Scholar, PubMed, Sci Finder, Reaxys, and Cochrane.

EVALUATION OF HERBAL MEDICINES AND ANIMAL EXPERIMENTATION

Over time, the use of herbal medicines has increased rapidly. This is influenced by several main factors, including the relatively cheap price and avoiding concerns about the side effects of chemical drugs. In practice, screening tests need to be carried out on a drug product that will be marketed, one of which is through a toxicity test. The use of animal models as experimental materials provides invaluable information in many aspects of pathophysiology, treatment, and diagnosis of human disease. Without exception, research on traditional ingredients also relies heavily on animals in in vivo, in situ, and in vitro experiments. This study uses a literature review with a descriptive approach based on secondary literature derived from Google Scholar, PubMed, and Science Direct. Research conducted on animals regarding herbal medicine can provide valuable insights into a herbal remedy. Selecting the appropriate animal for a study is crucial to obtain scientifically convincing results. Animals used for pharmacological studies should be standard species. Rodents, guinea pigs, rabbits, cats, and dogs are often used in traditional herbal medicine research. Moreover, herbal materials used for pharmacological research should be standardized to control quality and ensure the reproducibility of experimental outcomes. The standardization of herbal medicine should encompass species identification (name, origin, description, and purity), extraction procedures, chemical analysis of major and bioactive compounds, heavy metals, pesticides, and storage stability.

Conservation and Exploration of the Potential of Rare Medicinal Plants in the Tropical Rainforest of Bukit Barisan, Sumatra, Indonesia: An Effort Towards Sustainable Herbal Medicine

The Bukit Barisan tropical rainforest in Sumatra, Indonesia, is one of the most biodiverse areas in the world. It is estimated that there are more than 10,000 plant species in this forest, and many of them have potential as herbal medicines. However, deforestation and overexploitation threaten the preservation of medicinal plants in the Bukit Barisan tropical rainforest. This causes loss of valuable natural resources and hinders research and development of new herbal medicines. This research was conducted in several tropical rainforests in Bukit Barisan, Sumatra. Field surveys were conducted to document rare medicinal plant species. Plant samples were collected and analyzed for their phytochemical content. Bioassay tests were carried out to evaluate antibacterial, antioxidant and anti-inflammatory activities. Strategies for conservation and sustainable exploration of rare medicinal plants are developed based on research results. Field surveys found 27 species of rare medicinal plants. Phytochemical analysis shows that this plant contains various bioactive compounds, such as alkaloids, flavonoids and terpenoids. Bioassay tests show that this plant has significant antibacterial, antioxidant and anti-inflammatory activity. In conclusion, the Bukit Barisan tropical rainforest has great potential for the development of herbal medicine. Sustainable conservation and exploration of rare medicinal plants in the Bukit Barisan tropical rainforest is important to ensure the preservation of these valuable natural resources and to improve community health.

Anatomical studies on the PES region of Zebu cattle (Bos Taurus indicus) with special references to 3D computed tomography imaging technique

The 3D render volume reconstruction CT (3D-RVCT) produced detailed images of the PES region, determining its relationships with the surrounding structures. Despite extensive research in veterinary studies on the PES through gross anatomy and CT, there is a lack of studies on the PES of zebu cattle. The study aimed to analyze the PES of Zebu cattle using gross cross-sectional, radiographic, CT, and morphometric methods, with the use of 3D-RVCT to provide anatomical guidance for surgeons and students. The study was performed on sixteen PES regions to provide hard and soft tissues in CT images. Three are five tarsal bones and two large fused (III and IV) metatarsal bones that were completely fused except for their distal extremities, which were divided distally by the intertrochlear notch. The cortical thickness of the metatarsal bone was equal on both sides. The bony septum divided the medullary cavity between the two fused large metatarsal bones in the proximal distal half only and disappeared in the middle part. The reconstruction showed similar sizes in the right and left limbs, confirming the pes bones. The radiographic and CT images could be used as a normal reference for the interpretation of some clinical diseases in the PES. The 3D CT reconstruction of the pes bones was described by various CT oblique dorsal and plantar views. The study focuses on diagnosing PES disorders using CT imaging, improving medical interventions, improving Zebu cattle health outcomes, and empowering students to contribute to veterinary medicine research and advancements.

Two new endophytic fungi of Colletotrichum and Diaporthe isolated from Berchemia polyphylla var. leioclada in Guizhou Province, China

Berchemia polyphylla var. leioclada is an important traditional Chinese medicinal plant, it has been proved to produces a variety of unique metabolites, such as glycosides, quinones, lignans, terpenes and flavonoids, with different bioactivities including antioxidant, anti-tumor, anti-diarrheal, anti-inflammatory, analgesic and antibacterial activities. Studies showed that endophytic fungi may secrete compounds that are similar to those of the host. Thus, the endophytic fungi of medicinal plants are important medicinal resources and are beneficial to the research and development of natural medicines. Therefore, studying the diversity of endophytic fungi in the medicinal plant of Berchemia polyphylla var. leioclada is of great significance to discovering new drugs. However, the endophytic fungi in Berchemia polyphylla var. leioclada have been poorly studied. This study investigates the endophytic fungi in Berchemia polyphylla var. leioclada from Guizhou Province, China. Two new species Diaporthe berchemiae and Colletotrichum berchemiae are introduced based on morphological characters and multi-locus phylogenetic analysis. This is the first report of endophytic fungi in the medicinal plant Berchemia polyphylla var. leioclada, which enhances our understanding of the endophytic fungi in the medicinal plant Berchemia polyphylla var. leioclada.

Underutilized Medicinal Plant in Ethiopia: The Case of Aloe Species

Ethiopian aloe species are known for traditional medicine for both human and livestock as well as for the preparation of various cosmetic products such as soap and lotion. The aloe species contributed great economic and social benefits for many local communities. In recent years, there has been a growing interest in the use of aloe species in the beauty and wellness industry. Many international companies have started to source aloe from Ethiopia, recognizing its high quality and potency. However, there are concerns about the sustainability of aloe harvesting in Ethiopia. Due to the high demand for aloe products, there has been an increase in over-harvesting without replanting and unsustainable practices. This has led to a decline in some aloe species that hastens the need for better management and conservation efforts. Government and non-government groups should pay attention in order to minimize the damage to the aloe species. Traditional medicine practitioners, research institutes, and universities as well as biodiversity conservation institutes should give attention to the valuable aloe species in the country. As the species are declining from time to time, the devotions of the Ministry of Agriculture, Ministry of Labor and Skill, and Biotechnology Institute are essential to ensure the sustainability and proper uses of these valuable plants for future generations.

The Application of Artificial Intelligence in the Research and Development of Traditional Chinese Medicine

Review The Application of Artificial Intelligence in the Research and Development of Traditional Chinese Medicine Zhipeng Ke 1,2, Minxuan Liu 1,2,3, Jing Liu 1,2, Zhenzhen Su 1,2, Lu Li 1,2, Mengyu Qian 1,2, Xinzhuang Zhang 1,2, Tuanjie Wang 1,2, Liang Cao 1,2, Zhenzhong Wang 1,2, and Wei Xiao 1,2, * 1 National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Lianyungang 222106, China 2 Jiangsu Kanion Pharmaceutical Co., Ltd, Lianyungang 222104, China 3 ‍School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210009, China * Correspondence: xw_kanion@163.com Received: 4 September 2023 Accepted: 4 November 2023 Published: 6 March 2024 Abstract: With the accumulation of data in the pharmaceutical industry and the development of artificial intelligence technology, various artificial intelligence methods have been successfully employed in the drug discovery process. The integration of artificial intelligence in Traditional Chinese medicine has also gained momentum, encompassing quality control of Chinese patent medicines, prescriptions optimization, discovery of effective substances, and prediction of side effects. However, artificial intelligence also faces challenges and limitations in Traditional Chinese medicine development, such as data scarcity and complexity, lack of interdisciplinary professionals, black-box models, etc. Therefore, more research and collaboration are needed to address these issues and explore the best ways to integrate artificial intelligence and Traditional Chinese medicine to improve human health.

Long read sequencing on its way to the routine diagnostics of genetic diseases.

The clinical application of technological progress in the identification of DNA alterations has always led to improvements of diagnostic yields in genetic medicine. At chromosome side, from cytogenetic techniques evaluating number and gross structural defects to genomic microarrays detecting cryptic copy number variants, and at molecular level, from Sanger method studying the nucleotide sequence of single genes to the high-throughput next-generation sequencing (NGS) technologies, resolution and sensitivity progressively increased expanding considerably the range of detectable DNA anomalies and alongside of Mendelian disorders with known genetic causes. However, particular genomic regions (i.e., repetitive and GC-rich sequences) are inefficiently analyzed by standard genetic tests, still relying on laborious, time-consuming and low-sensitive approaches (i.e., southern-blot for repeat expansion or long-PCR for genes with highly homologous pseudogenes), accounting for at least part of the patients with undiagnosed genetic disorders. Third generation sequencing, generating long reads with improved mappability, is more suitable for the detection of structural alterations and defects in hardly accessible genomic regions. Although recently implemented and not yet clinically available, long read sequencing (LRS) technologies have already shown their potential in genetic medicine research that might greatly impact on diagnostic yield and reporting times, through their translation to clinical settings. The main investigated LRS application concerns the identification of structural variants and repeat expansions, probably because techniques for their detection have not evolved as rapidly as those dedicated to single nucleotide variants (SNV) identification: gold standard analyses are karyotyping and microarrays for balanced and unbalanced chromosome rearrangements, respectively, and southern blot and repeat-primed PCR for the amplification and sizing of expanded alleles, impaired by limited resolution and sensitivity that have not been significantly improved by the advent of NGS. Nevertheless, more recently, with the increased accuracy provided by the latest product releases, LRS has been tested also for SNV detection, especially in genes with highly homologous pseudogenes and for haplotype reconstruction to assess the parental origin of alleles with de novo pathogenic variants. We provide a review of relevant recent scientific papers exploring LRS potential in the diagnosis of genetic diseases and its potential future applications in routine genetic testing.

Setting a dutch integrative medicine research agenda: Results of a consensus-based strategy

IntroductionThe WHO Traditional Medicine Strategy 2014–2023 emphasises the significance of traditional medicine systems for preventing and treating diseases, worldwide. As a result, many countries have developed national research programmes and research institutes dealing with traditional, complementary and integrative medicine (TCIM) (WHO Global Report on Traditional and Complementary Medicine, Geneva, 2019) or integrative medicine (IM). Despite considerable public interest in IM in the Netherlands, no Dutch programme or research institute has been established, yet. In 2018, a consortium for integrative care and health was founded, and developed a national research agenda with research priorities for the Netherlands. MethodsThe consensus-based strategy for developing the research agenda involved: (1) conducting a literature review, (2) organising an online consensus meeting with a select group of integrative medicine (IM) experts, (3) conducting a survey among IM stakeholders, and (4) organising a second consensus meeting with the same group of IM experts to discuss the survey results and further refine the research agenda. Snowball sampling was used to recruit IM stakeholders, starting from a list of those interested in or connected to IM. ResultsNinety-two stakeholders completed the survey. The most promising research areas were oncology, pain management and palliative care. Respondents awarded the highest priority to research on the effectiveness, cost-effectiveness and safety of IM interventions. Directions for research included mind–body interventions, biological interventions and whole medical systems. Moreover, respondents strongly recommended developing reliable patient information tools. Facilitators for IM implementation were increasing attention on prevention, the rising incidence of chronic diseases and the shift from disease-focused to health-focused approaches. The identified barriers included a lack of knowledge about IM, the absence of health insurance reimbursement for complementary medicine, and governance structures of healthcare organisations. ConclusionsThe first Dutch IM research agenda was developed based on consensus among Dutch healthcare professionals, along with input from a smaller group of patients and researchers. This agenda provides clear research directions and distinguishes both positive developments and barriers for IM in the Netherlands.