Recent Advances Research Articles

A Complete Overview of the Polycystic Ovarian Syndrome with Recent Advancement in Clinical Trial

Background: Polycystic ovarian syndrome (PCOS) has emerged as one of the most common endocrine and metabolic disorders seen in women of childbearing age throughout the whole world. The complex pathophysiology, different diagnostic criteria, and various manifestations attached to several environmental factors, including lifestyle influences, have made it one of the most difficult disorders to treat in recent times. In addition, inadequate knowledge among patients and a lack of dedicated approved medications have only enhanced the difficulties in treating such a heterogeneous disorder. Objective: The main objective of this review-type paper is to provide a detailed overview of PCOS along with the current concept of a clinical stance in this complex multigenic disorder. Method: The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents, the keywords “PCOS; hirsutism; psychological burden; obesity” and others of a similar nature were utilized. Conclusion: PCOS is a complicated hormonal, metabolic, and psychological condition with many different clinical manifestations. It is among the most prevalent causes of infertility. Before considering any medication choices, lifestyle modifications should be considered the primary therapeutic prescription for PCOS-related infertility. According to recent studies, PCOS does not affect the risk of ovarian or breast cancer, but it does raise the risk of endometrial cancer in women of all ages. These results suggest that PCOS may increase the risk of gynaecological cancer morbidity. The following stage is ovulation stimulation, which is best accomplished with letrozole and is followed by clomiphene citrate. Women who had not responded to the first-line oral ovulatory medicine were given gonadotropins as a backup. Early detection of girls with a high propensity to develop PCOS will be made possible by a comprehensive knowledge of the condition's etiology. Adolescent PCOS will be better managed overall, related comorbidities will be prevented, and quality of life will increase with customized therapeutic approaches.

The Emergence of Nanotechnology in the Prognosis and Treatment of Myocardial Infarctions.

Myocardial infarction (MI), commonly known as a heart attack, is a critical cardiovascular condition associated with high morbidity and mortality rates worldwide. Despite significant advancements in traditional treatment modalities, there remains a need for innovative approaches to improve the prognosis and treatment outcomes of MI. The emergence of nanotechnology has provided a promising avenue for revolutionizing the management of this life-threatening condition. This manuscript aims to explore the role of nanotechnology in the prognosis and treatment of myocardial infarctions. Nanotechnology offers unique advantages in the field of cardiovascular medicine, including targeted drug delivery, precise imaging and diagnosis, regenerative medicine approaches, biosensors and monitoring, and the integration of therapy and diagnostics (theragnostic). One of the key advantages of nanotechnology is the ability to deliver therapeutic agents directly to the affected site. Nanoparticles can be engineered to carry drugs specifically to damaged heart tissue, enhancing their efficacy while minimizing off-target effects. Additionally, nanoparticles can serve as contrast agents, facilitating high-resolution imaging and accurate diagnosis of infarcted heart tissue. Furthermore, nanotechnology-based regenerative approaches show promise in promoting tissue healing and regeneration after MI. Nanomaterials can provide scaffolding structures or release growth factors to stimulate the growth of new blood vessels and support tissue repair. This regenerative potential holds significant implications for restoring cardiac function and minimizing long-term complications. Nanotechnology also enables real-time monitoring of critical parameters within the heart, such as oxygen levels, pH, and electrical activity, through the utilization of nanoscale devices and sensors. This capability allows for the early detection of complications and facilitates timely interventions. Moreover, the integration of therapy and diagnostics through nanotechnology- based platforms, known as theragnostic, holds tremendous potential. Nanoparticles can simultaneously deliver therapeutic agents while providing imaging capabilities, enabling personalized treatment strategies tailored to individual patients. This manuscript will review the recent advancements, clinical trials, and patents in nanotechnology for the prognosis and treatment of myocardial infarctions. By leveraging nanotechnology's unique properties and applications, researchers and clinicians can develop innovative therapeutic approaches that enhance patient outcomes, improve prognosis, and ultimately revolutionize the management of myocardial infarctions.

Multi-modal Language models in bioacoustics with zero-shot transfer: a case study

Automatically detecting sound events with Artificial Intelligence (AI) has become increas- ingly popular in the field of bioacoustics, ecoacoustics, and soundscape ecology, particularly for wildlife monitoring and conservation. Conventional methods predominantly employ supervised learning techniques that depend on substantial amounts of manually annotated bioacoustic data. However, manual annotation in bioacoustics is tremendously resource- intensive in terms of both human labor and financial resources, and it requires considerable domain expertise. Moreover, the supervised learning framework limits the application scope to predefined categories within a closed setting. The recent advent of Multi-Modal Language Models has markedly enhanced the versatility and possibilities within the realm of AI appli- cations, as this technique addresses many of the challenges that inhibit the deployment of AI in real-world applications. In this paper, we explore the potential of Multi-Modal Language Models in the context of bioacoustics through a case study. We aim to showcase the potential and limitations of Multi-Modal Language Models in bioacoustic applications. In our case study, we applied an Audio-Language Model–—a type of Multi-Modal Language Model that aligns language with audio / sound recording data—–named CLAP (Contrastive Language–Audio Pretraining) to eight bioacoustic benchmarks covering a wide variety of sounds previously unfamiliar to the model. We demonstrate that CLAP, after simple prompt engineering, can effectively recognize group-level categories such as birds, frogs, and whales across the benchmarks without the need for specific model fine-tuning or additional training, achieving a zero-shot transfer recognition performance comparable to supervised learning baselines. Moreover, we show that CLAP has the potential to perform tasks previously unattainable with supervised bioacoustic approaches, such as estimating relative distances and discovering unknown animal species. On the other hand, we also identify limitations of CLAP, such as the model’s inability to recognize fine-grained species-level categories and the reliance on manually engineered text prompts in real-world applications.

Comprehensive biomarker profiles in hematological malignancies: improving diagnosis, prognosis, and treatment.

Hematological malignancies present substantial challenges in clinical practice due to their heterogeneity and complex biological profiles. In these diseases, biomarkers - measurable indicators of biological states - are indispensable for diagnosis, prognosis, and therapeutic decision-making. Emerging biomarkers are significantly improving outcomes in hematological cancers by enhancing early detection, refining prognostic assessments, enabling personalized treatment approaches, and optimizing overall patient management. This progress translates into better clinical outcomes and more effective strategies to treat and manage malignancies. The field of biomarker discovery has developed from basic morphological and cytogenetic markers to advanced molecular techniques, including polymerase chain reaction (PCR) and next-generation sequencing (NGS), which have significantly enhanced diagnostic accuracy and led to the development of targeted therapies. Additionally, the recent advent of technologies like mass spectrometry and single-cell RNA sequencing enables comprehensive molecular profiling and reveals novel biomarkers that were previously undetectable. Our aim in this manuscript is to provide a comprehensive overview of recent and novel immunohematological biomarkers, their diagnostic and therapeutic applications, and the future directions of this field.

Artificial intelligence in healthcare: A survival guide for internists

Artificial intelligence (AI) is experiencing considerable growth in medicine, driven by the explosion of available biomedical data and the emergence of new algorithmic architectures. Applications are rapidly multiplying, from diagnostic assistance to disease progression prediction, paving the way for more personalized medicine. The recent advent of large language models, such as ChatGPT, has particularly interested the medical community, thanks to their ease of use, but also raised questions about their reliability in medical contexts. This review presents the fundamental concepts of medical AI, specifically distinguishing traditional discriminative approaches from new generative models. We detail the different exploitable data sources and methodological pitfalls to avoid during the development of these tools. Finally, we address the practical and ethical implications of this technological revolution, emphasizing the importance of the medical community's appropriation of these tools.

Application of Animal Models to Study Infectious Diseases

Infectious diseases, which are caused by microorganisms such as bacteria, viruses, fungi, or parasites, can be contracted from other people, the environment, animal contact, or insect bites. Infectious diseases are becoming escalating concerns, mainly due to increasing antibiotic resistance. These disorders remain one of the primary causes of human mortality. Due to the lack of human data on new emerging diseases, ethical values, and the lethal risk of these pathogens, animal models are often recommended for experimental re- search on these diseases. According to the similarities between humans and animals in physiology, genetics, anatomy, availability, ease of handling, and production rate, scientists evaluate different medical problems in animal models before applying their findings to humans. According to the recent advent of the isolation of novel microorganisms, researchers must challenge the infectious ability of microorganisms in the biological system of animal models. An infectious disease animal model attempts to mimic the host-pathogen inter- action. Accordingly, a disease model is defined by both the host and pathogen combination. In this review article, we aimed to discuss various animal models established for studying different infectious diseases.

Recent Advances in Cutaneous Carcinoma Therapy Through Integrated Use of Immunotherapy and Nanotechnology.

Skin cancer is one of the most lethal cancers today, posing significant challenges to public health and potentially impacting global health and economic stability. Due to its high rate of incidence, innovative and effective treatments are crucial. Among these, immunothera-peutic approaches have emerged as transformative, offering new hope by harnessing the body's immune system to target and eliminate cancerous cells. Immunotherapy has changed the treatment landscape for skin cancer, providing options such as checkpoint inhibitors and adoptive cell transfer therapies that specifically enhance immune activity against tumors. De-spite these advancements, the broader adoption of immunotherapeutic modalities is challeng-ing due to concerns about their toxicity and variable efficacy. The side effects, such as im-mune-related adverse events, can be severe and sometimes limit their use. In response to these challenges, nanotechnology in cancer treatment has gained significant attention. Nanotechnol-ogy-based approaches show promise in improving the delivery and effectiveness of cancer therapies, particularly for skin cancer immunotherapy. Nanoparticles can deliver therapeutic agents directly to tumors, minimizing systemic toxicity and enhancing treatment precision. These strategies also boost the immune system's ability to target cancer cells while overcom-ing the limitations of current immunotherapies. This review explores various anticancer thera-peutic approaches for managing skin cancer, focusing on immunotherapy and its challenges. It highlights how integrating nanotechnology with cancer immunotherapy offers a promising av-enue for enhancing treatment efficacy and safety. The review also provides an overview of re-cent advancements in skin cancer treatment, showcasing how these innovative strategies are paving the way for more effective and less toxic therapeutic options in combating one of the deadliest cancers.

Dysbiosis of Oral Microbiome: A Key Player in Oral Carcinogenesis? A Critical Review.

The oral cavity is known to harbor hundreds of microorganisms, belonging to various genera, constituting a peculiar flora called the oral microbiome. The change in the relative distribution of the constituents of this microbial flora, due to any reason, leads to oral dysbiosis. For centuries, oral dysbiosis has been linked to the etiopathogenesis of several medical illnesses, both locally and systemically-. However, aided by the recent advent of bio-technological capabilities, several reports have re-emerged that link oral dysbiosis to oral carcinogenesis, and numerous studies are currently exploring their association and plausible mechanisms. Some of the proposed mechanisms of oral dysbiosis-induced carcinogenesis (ODIC) include-a bacteria-induced chronic inflammatory state leading to direct cellular damage, inflammatory-cytokine-mediated promotion of cellular proliferation and invasion, release of bacterial products that are carcinogenic, and suppression of local immunity by alteration of the tumor microenvironment. However, the actual interactions between these cellular mechanisms and their role in carcinogenesis are not yet fully understood. This review provides a comprehensive overview of the various hypotheses and mechanisms implicated in the ODIC, along with the corresponding molecular aberrations. Apart from discussing the usual constituents of the oral microbiome profile, the review also summarizes the various dysbiosis profiles implicated in ODIC. The review also sheds light on the potential clinical implications of the research on oral microbiome in the prevention and management of oral cancer.

Make-Your-Video: Customized Video Generation Using Textual and Structural Guidance.

Creating a vivid video from the event or scenario in our imagination is a truly fascinating experience. Recent advancements in text-to-video synthesis have unveiled the potential to achieve this with prompts only. While text is convenient in conveying the overall scene context, it may be insufficient to control precisely. In this paper, we explore customized video generation by utilizing text as context description and motion structure (e.g. frame- wise depth) as concrete guidance. Our method, dubbed Make-Your-Video, involves joint-conditional video generation using a Latent Diffusion Model that is pre-trained for still image synthesis and then promoted for video generation with the introduction of temporal modules. This two-stage learning scheme not only reduces the computing resources required, but also improves the performance by transferring the rich concepts available in image datasets solely into video generation. Moreover, we use a simple yet effective causal attention mask strategy to enable longer video synthesis, which mitigates the potential quality degradation effectively. Experimental results show the superiority of our method over existing baselines, particularly in terms of temporal coherence and fidelity to users' guidance. In addition, our model enables several intriguing applications that demonstrate potential for practical usage. The code, model weights, and videos are publicly available at our project page: https://doubiiu.github.io/projects/Make-Your-Video/.

Recent Developments in Nanotechnology and Immunotherapy for the Diagnosis and Treatment of Pancreatic Cancer.

Pancreatic cancer kills millions of people worldwide each year and is one of the most prevalent causes of mortality that requires prompt therapy. A large number of people suffering from pancreatic cancer are detected at an advanced stage, with incurable and drug-resistant tumor, hence the overall survival rate of pancreatic cancer is less. The advance phase of this cancer is generated because of expression of the cancer-causing gene, inactivation of the tumorsuppressing gene, and deregulation of molecules in different cellular signalling pathways. The prompt diagnosis through the biomarkers significantly evades the progress and accelerates the survival rates. The overexpression of Mesothelin, Urokinase plasminogen activator, IGFR, Epidermal growth factor receptor, Plectin-1, Mucin-1 and Zinc transporter 4 were recognized in the diagnosis of pancreatic cancer. Nanotechnology has led to the development of nanocarriersbased formulations (lipid, polymer, inorganic, carbon based and advanced nanocarriers) which overcome the hurdles of conventional therapy, chemotherapy and radiotherapy which causes toxicity to adjacent healthy tissues. The biocompatibility, toxicity and large-scale manufacturing are the hurdles associated with the nanocarriers-based approaches. Currently, Immunotherapybased techniques emerged as an efficient therapeutic alternative for the prevention of cancer. Immunological checkpoint targeting techniques have demonstrated significant efficacy in human cancers. Recent advancements in checkpoint inhibitors, adoptive T cell therapies, and cancer vaccines have shown potential in overcoming the immune evasion mechanisms of pancreatic cancer cells. Combining these immunotherapeutic approaches with nanocarriers holds great promise in enhancing the antitumor response and improving patient survival.

Light Sensitive Liposomes: A Novel Strategy for Targeted Drug Delivery.

Light-sensitive liposomes have emerged as a promising platform for drug delivery, offering the potential for precise control over drug release and targeted therapy. These lipid-based nanoparticles possess photoresponsive properties, allowing them to undergo structural changes or release therapeutic payloads upon exposure to specific wavelengths of light. This review presents an overview of the design principles, fabrication methods, and applications of light-sensitive liposomes in drug delivery. Further, this article also discusses the incorporation of light-sensitive moieties, such as azobenzene, spiropyran, and diarylethene, into liposomal structures, enabling spatiotemporal control over drug release. The utilization of photosensitizers and imaging agents to enhance the functionality and versatility of light-sensitive liposomes is also highlighted. Finally, the recent advances, challenges, and future directions in the field, emphasizing the potential for these innovative nanocarriers to revolutionize targeted therapeutics, are also discussed.

Microfluidics-assisted Tumor Cell Separation Approaches for Clinical Applications: An Overview on Emerging Devices.

Recent advances in science and technology have led to revolutions in many different scientific and industrial fields. The term lab on a chip, or in other word, performing a variety of complex analyzes in just a short time and in a very small space, is a term that has become very common in recent years, and what used to be a dream has now come to life in practice. In this paper, we has been tried to investigate a specific type of lab technology on a chip, which is of course one of the most common, namely the knowledge and technology of cell separation by using microfluidic technique that can be separated based on size and deformation, adhesion and electrical properties. The tissue of the human body is degraded due to injury or aging, which is often tried to treat this tissue disorder by using drugs, but they are not always enough. Stem cell-based medicine is a novel form of medicine which promises the restoration or regeneration of tissues and functioning organs. Although many models of microfluidic systems have been designed for cell separation, the choice of appropriate device to achieve a reliable result is presented as a challenge. So, in this study, Fluorescence Activated Cell Sorting (FACS), Dielectrophoresis (DEP), Magnetic Activated Cell Sorting (MACS) and Acoustic microfluidic system are four distinct categories of active microfluidic systems explored. Also, the advantages, disadvantages and the current status of the mentioned devices in these methods, are reviewed.

From Vision Correction to Drug Delivery: Unraveling the Potential of Therapeutic Contact Lens.

Contact lenses (CLs) have become an essential tool in ocular drug delivery, providing effective treatment options for specific eye conditions. In recent advancements, Therapeutic CLs (TCLs) have emerged as a promising approach for maintaining therapeutic drug concentrations on the eye surface. TCLs offer unique attributes, including prolonged wear and a remarkable ability to enhance the bioavailability of loaded medications by more than 50%, thus gaining widespread usage. They have proven beneficial in pain management, medication administration, corneal healing, and protection. To achieve sustained drug delivery from TCLs, researchers are exploring diverse systems, such as polymeric nanoparticulate systems, lipidic systems, and the incorporation of agents like vitamin E or rate-limiting polymers. However, despite breakthrough successes, certain challenges persist, including ensuring drug stability during processing and manufacturing, controlling release kinetics, and biomaterial interaction, reducing protein adhesion, and addressing drug release during packaging and storage etc. While TCLs have shown overall success in treating corneal and ocular surface disorders, careful consideration of potential issues and contraindications is vital. This review offers an insightful perspective on the critical aspects that need to be addressed regarding TCLs, with a specific emphasis on their advantages and limitations.

Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review.

Innovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.

Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.

Ovarian cancer is the fifth leading cause of mortality and the most lethal gynecologic malignancy among females. It may arise from atypical borderline tumors (Type I) or serous tubal intraepithelial carcinoma (Type II). The diagnosis of cancer at its early stages is difficult because of non-specific symptoms, most patients are diagnosed at the advanced stage. Several drugs and therapeutic strategies are available to treat ovarian cancer such as surgery, chemotherapy, neoadjuvant therapy, and maintenance therapy. However, the cancer cells have developed resistance to a number of available therapies causing treatment failure. This emerging chemoresistance in ovarian cancer cells is becoming an obstacle due to alterations in multiple cellular processes. These processes involve altered drug target response, drug pumps, detoxification systems, lower sensitivity to apoptosis, and altered proliferation, and are responsible for developing resistance to anticancer medicines. Various research reports have evidenced that these altered processes might play a role in the emergence of resistance. This review addresses the recent advances in understanding the underlying mechanisms of ovarian cancer resistance and covers sophisticated alternative pathways to overcome these resistance mechanisms in patients.

In Rheumatoid Arthritis, A Review of ncRNAs Related to NF-κB Signaling Pathways.

Rheumatoid arthritis (RA) is an autoimmune disease with no known cure that results in joint deformities and dysfunction, significantly impacting the quality of life of patients. The abnormal NF-ＫB signaling pathway in RA has emerged as a crucial research area for the development of RA therapies, with non-coding RNAs (ncRNAs) serving as a potentially meaningful avenue to regulate it. Thus, understanding the role of ncRNAs in RA and the identification of new therapeutic targets have become pressing issues in the field. In this review, we aim to summarize recent studies on ncRNAs that regulate the NF-ＫB signaling pathway in RA, including miRNAs, lncRNAs, and circRNAs, as well as the mechanisms by which drugs modulate NF-Ｋ B activity. By highlighting these recent advances, we hope to promote further research into targeted RA therapy and provide novel directions and ideas for researchers in the field.

Neural substrates of cold nociception in Drosophila larva.

Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in Drosophila larvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validated Drosophila larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back) and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. Further, we demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Finally, we characterize the premotor to motor neuron network underlying cold-evoked CT and delineate the muscular basis of CT response. Collectively, we demonstrate how Drosophila larvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus-specific behaviors.

Molecular-targeted Therapy for Precision Medicine in Gastrointestinal Cancer: Advancement in Cancer Targeting Strategies.

Gastrointestinal (GI) cancer represent significant health challenges, affecting the digestive system with often subtle symptoms that can delay diagnosis. GI cancers account for a higher global mortality rate than any other cancer, largely due to the limited availability of highly effective treatment options." Due to next-generation sequencing and new preclinical model tools, that we have learned more regarding its pathophysiology and molecular changes. Every molecular subtype has been characterised molecularly and new treatment targets have been found. Furthermore, tumour xenografts and organoids are grown from patients and are increasingly powerful resources for investigating GI patients' genetic evolution, identifying biomarkers, screening drugs, and conducting preclinical evaluations of personalised medicine approaches. Gastrointestinal (GI) cancer research is rapidly evolving, with recent advance-ments in precision medicine and immunotherapy offering new treatment options. Cutting-edge therapies, such as immune checkpoint inhibitors and targeted therapies like BRAF and HER2 inhibitors, are showing promise in treating specific types of GI cancers. These changes are making it possible for the age of precision medicine to use a mix of clinical, genome-based, and phenotype-based methods to diagnose and treat each GI patient individually. Clin-ical trials are exploring novel combinations of therapies to enhance survival rates and reduce side effects for patients with GI cancers, including colorectal, gastric, and pancreatic cancers. These developments are reshaping the future of gastrointestinal oncology. The purpose of this review is to study the current state of knowledge about predictive biomarkers, prospective novel targeted treatments, potential causes of conflicting trial outcomes, and the prospects for precision medicine in gastric cancer in the future.

Genetic testing results of retinal dystrophies in a diverse population: impact of race and ethnicity

ABSTRACT Introduction Due to the recent advent of gene-targeted retinal therapies, the clinical value of high-yield genetic testing for inherited retinal dystrophies (IRDs) has increased considerably. However, diagnostic yield is limited by the reported patient populations in allele frequency databases. This study aimed to determine the effect of race and ethnicity on diagnostic yield in IRDs. Methods Retrospective review of individuals with suspected IRD based on clinical findings or diagnosis of associated syndrome who underwent genetic testing between 2009 and 2021. Self-reported race and ethnicity, ophthalmic examination findings, ERG results, and genetic testing findings were collected and analyzed. Results In 93 individuals (90 families) with suspected IRD, the diagnostic yield was 72% (67 individuals). The rate of diagnostic yield was not significantly associated with family history, associated syndromes, age at testing, ERG results, or ophthalmic exam findings. Further, higher rates of positive diagnostic yield were not associated with more recent genetic testing. There was a trend toward differences in diagnostic yield between races (77% White, 65% Other, 64% Asian, 50% Black) and ratio of pathogenic/likely pathogenic (P/LP) variants to variants of unknown significance (46%:54% White, 36%:64% Other, 31%:69% Asian, 30%:70% Black). Conclusions Current genetic testing for IRDs trends toward higher diagnostic yield and identification of P/LP variants in patients identifying as White compared to other races. In order to prevent negative impacts on access to gene-targeted trials and treatments for non-White patients, wider genetic testing in diverse populations is required to create comprehensive catalogs of gene variants associated with IRDs.

Machine learning-based analysis of microfluidic device immobilized C. elegans for automated developmental toxicity testing

Developmental toxicity (DevTox) tests evaluate the adverse effects of chemical exposures on an organism’s development. Although current testing primarily relies on large mammalian models, the emergence of new approach methodologies (NAMs) is encouraging industries and regulatory agencies to evaluate novel assays. C. elegans have emerged as NAMs for rapid toxicity testing because of its biological relevance and suitability to high throughput studies. However, current low-resolution and labor-intensive methodologies prohibit its application for sub-lethal DevTox studies at high throughputs. With the recent advent of the large-scale microfluidic device, vivoChip, we can now rapidly collect 3D high-resolution images of ~ 1000 C. elegans from 24 different populations. While data collection is rapid, analyzing thousands of images remains time-consuming. To address this challenge, we developed a machine-learning (ML)-based image analysis platform using a 2.5D U-Net architecture (vivoBodySeg) that accurately segments C. elegans in images obtained from vivoChip devices, achieving a Dice score of 97.80%. vivoBodySeg processes 36 GB data per device, phenotyping multiple body parameters within 35 min on a desktop PC. This analysis is ~ 140 × faster than the manual analysis. This ML approach delivers highly reproducible DevTox parameters (4–8% CV) to assess the toxicity of chemicals with high statistical power.