Specific Tissues Research Articles

Recent Advances in Pharmaceutical Design: Unleashing the Potential of Novel Therapeutics.

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

Nanorevolution Unleashing the Power of Nanotechnology

Abstract: Nanotechnology, the manipulation of matter at the nanoscale, has been an extraordi-nary scientific frontier that has revolutionized various fields, with one of the most promising ap-plications being in the realm of medicine. Nanomedicine, an interdisciplinary field at the intersec-tion of nanotechnology and medicine, holds tremendous potential to transform the landscape of healthcare, diagnosis, and treatment. This abstract delves into the burgeoning advancements of nanotechnology in nanomedicine, highlighting its significance, potential benefits, and ethical con-siderations. The primary focus of nanomedicine is to engineer and utilize nanoscale materials, such as nano-particles and nanostructures, to improve the effectiveness and precision of medical interventions. Nano-sized drug delivery systems can target specific cells or tissues, enhancing therapeutic out-comes and reducing side effects. These nanocarriers can penetrate biological barriers and accu-mulate at disease sites, enabling more efficient drug delivery and increasing the bioavailability of therapeutic agents. Furthermore, nanotechnology has opened new horizons in medical imaging. Nanoparticles can be engineered to be responsive to certain diseases or conditions, providing val-uable information for early detection and precise diagnosis. Novel contrast agents based on na-nomaterials have the potential to revolutionize imaging techniques, offering higher sensitivity and specificity, ultimately leading to improved patient outcomes. Beyond diagnostics and drug delivery, nanotechnology is fostering breakthroughs in regenerative medicine. Nanomaterials can act as scaffolds, guiding tissue repair and promoting cellular regen-eration. By harnessing the unique properties of nanoscale materials, tissue engineering, and organ transplantation may witness unparalleled advancements, bringing hope to countless patients awaiting life-saving treatments. However, the unprecedented potential of nanomedicine also rais-es ethical concerns that demand careful consideration. As nanotechnology progresses, concerns about the safety of nanomaterials, potential toxicity, and long-term effects must be addressed to ensure responsible and sustainable development.

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Nanotechnology-Based Approaches for Nose-to-Brain Drug Delivery in Neurodegenerative Diseases

: Drug delivery to the brain is a challenging task as many drugs do not cross the blood-brain barrier (BBB). As a result, designing strategies to target drugs to the brain requires significant effort. However, recent research has focused on the administration of drugs through the nose to the brain, a noninvasive way to bypass the BBB and deliver therapeutic molecules directly to the brain. Nose-to-brain drug delivery is a promising approach that allows for the direct transportation of therapeutic molecules to the brain while increasing drug concentration in the brain. This approach has gained considerable attention due to its non-invasive nature, which makes it feasible, reliable, and efficient. One promising approach for nose-to-brain drug delivery is the use of nanoparticles as a platform for drug and gene delivery. Nanoparticles offer several advantages, including the ability to protect therapeutic drugs from degradation and increase the efficacy of drug delivery due to their unique size, shape, and surface features. Nanoparticles can also be engineered to target specific cells or tissues, enabling more precise drug delivery to the brain. The use of nanoparticles for nose-to-brain drug delivery has been extensively studied, and recent developments have shown promising results. In addition, patents relating to medication targeting via the nasal route have been developed. These patents cover various aspects of drug delivery, including the use of different types of nanoparticles, methods for producing nanoparticles, and methods for delivering nanoparticles to the brain.

Morphological, mechanical and biological assessment of PCL/pristine graphene scaffolds for bone regeneration

Scaffolds are physical substrates for cell attachment, proliferation, and differentiation, ultimately leading to the regeneration of tissues. They must be designed according to specific biomechanical requirements such as mechanical properties, surface characteristics, biodegradability, biocompatibility, and porosity. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes. Polymeric scaffolds reinforced with electro-active particles could play a key role in tissue engineering by modulating cell proliferation and differentiation. This paper investigates the use of an extrusion additive manufacturing system to produce PCL/pristine graphene scaffolds for bone tissue applications. PCL/pristine graphene blends were prepared using a melt blending process. Scaffolds with regular and reproducible architecture were produced with different concentrations of pristine graphene. Scaffolds were evaluated from morphological, mechanical, and biological view. The results suggest that the addition of pristine graphene improves the mechanical performance of the scaffolds, reduces the hydrophobicity, and improves cell viability and proliferation.

Trojan Microparticles : A Composite Nanoparticle Delivery System

Abstract: In recent years, microparticulate systems have drawn growing attention as a viable strategy for delivering cells, proteins, and medications to target areas. The Nanoparticles-in-Microparticles System (NiMS) is a drug delivery method that combines nano- and microparticles to deliver medications or genes to particular bodily regions with precision. A promising method for achieving dual or multiple functions inside a formulation is the development of nanoparticle-in-microparticle systems (NiMS). NiMS comprises a microparticle (M.P.) matrix and one or more nanoparticles (N.P.s). The N.P.s can be designed to provide specific functionality, such as targeted drug delivery or imaging, while the M.P. matrix can be tailored to provide sustained release or protect the N.P.s from degradation. NiMS offer several advantages over traditional formulations, including the ability to control release profiles and achieve site-specific delivery. By combining different types of N.P.s and M.P.s, it is possible to create formulations that release drugs at different rates or with different kinetics, allowing for tailored treatment regimens. Additionally, by lowering off-target effects and boosting efficacy, the site-specific targeting offered by NiMS can enhance the therapeutic index of medications. Microparticles are small, micron-sized particles that can be loaded with therapeutic agents and designed to deliver them to specific tissues in the body. The pharmaceutical sector is developing microparticulate delivery systems for oral, pulmonary, and cutaneous administration. For instance, a promising strategy for treating respiratory conditions, including asthma and chronic obstructive pulmonary disease, is the development of inhalable microparticles (COPD). Moreover, the use of microparticles for topical drug delivery is being studied, where they can be formulated into creams, gels, or patches for treating skin disorders. The composition of microparticles is crucial for successful tissue regeneration because the particles must be biocompatible and able to interact with the cells in the targeted tissue. In addition, the size and shape of the particles can affect their behavior and how they interact with cells. Chemical and biological sensors and devices, optical detectors, electronic components, and nanoscale production depend on nanostructures because they offer unique properties, such as increased surface area and enhanced reactivity, which can be exploited to create more efficient and effective devices.

Beyond the Dusty Fog: Local Eye Drop Therapy and Potentially New Treatment Alternatives in Pseudoexfoliative Glaucoma.

Pseudoexfoliative glaucoma (PEG) is a type of secondary open-angle glaucoma characterized by the accumulation of whitish-gray material on the trabecular meshwork and lens, leading to an increase in intraocular pressure (IOP) and optic nerve damage. Local eye drop therapy is one of the first-line treatments for PEG, which include prostaglandin analogues, beta-blockers, and alpha-adrenergic agonists to lower IOP. New treatments beyond conventional techniques, however, are constantly being developed. One potential treatment proposed for PEG is based on magnetic phage display, which involves using magnetic nanoparticles conjugated to specific peptides or proteins selected using phage display techniques to remove aggregates in the anterior chamber of the eye or inflammatory cells and cytokines that contribute to PEG pathogenesis. Other potential treatments include microRNAs (miRNAs) that are involved in the regulation of gene expression at the post-transcription stages. Gene therapies, nanotechnology, immunotherapy and methods based on stem cells can also be potentially used to target and treat specific tissues and cells responsible for regulating IOP. In addition, photobiomodulation therapy (PBMT), a non-invasive procedure that utilizes low-level laser therapy to improve cellular function and promote tissue repair, can prove an interesting alternative in treating PEG. The aim of our mini-review is to provide a brief overview of these innovative methods that appear to offer potentially promising treatment options for PEG.

Critical Review: Uptake and Translocation of Organic Nanodelivery Vehicles in Plants.

Nanodelivery vehicles (NDVs) are engineered nanomaterials (ENMs) that, within the agricultural sector, have been investigated for their ability to improve uptake and translocation of agrochemicals, control release, or target specific tissues or subcellular compartments. Both inorganic and organic NDVs have been studied for agrochemical delivery in the literature, but research on the latter has been slower to develop than the literature on the former. Since the two classes of nanomaterials exhibit significant differences in surface chemistry, physical deformability, and even colloidal stability, trends that apply to inorganic NDVs may not hold for organic NDVs, and vice versa. We here review the current literature on the uptake, translocation, biotransformation, and cellular and subcellular internalization of organic NDVs in plants following foliar or root administration. A background on nanomaterials and plant physiology is provided as a leveling ground for researchers in the field. Trends in uptake and translocation are examined as a function of NDV properties and compared to those reported for inorganic nanomaterials. Methods for assessing fate and transport of organic NDVs in plants (a major bottleneck in the field) are discussed. We end by identifying knowledge gaps in the literature that must be understood in order to rationally design organic NDVs for precision agrochemical nanodelivery.

Impact of the Reduction Time-Dependent Electrical Conductivity of Graphene Nanoplatelet-Coated Aligned Bombyx mori Silk Scaffolds on Electrically Stimulated Axonal Growth.

Graphene-based nanomaterials, renowned for their outstanding electrical conductivity, have been extensively studied as electroconductive biomaterials (ECBs) for electrically stimulated tissue regeneration. However, using eco-friendly reducing agents like l-ascorbic acid (l-Aa) can result in lower conductive properties in these ECBs, limiting their full potential for smooth charge transfer in living tissues. Moreover, creating a flexible biomaterial scaffold using these materials that accurately mimics a specific tissue microarchitecture, such as nerves, poses additional challenges. To address these issues, this study developed a microfibrous scaffold of Bombyx mori (Bm) silk fibroin uniformly coated with graphene nanoplatelets (GNPs) through a vacuum coating method. The scaffold's electrical conductivity was optimized by varying the reduction period using l-Aa. The research systematically investigated how different reduction periods impact scaffold properties, focusing on electrical conductivity and its significance on electrically stimulated axonal growth in PC12 cells. Results showed that a 48 h reduction significantly increased surface electrical conductivity by 100-1000 times compared to a shorter or no reduction process. l-Aa contributed to stabilizing the reduced GNPs, demonstrated by a slow degradation profile and sustained conductivity even after 60 days in a proteolytic environment. β (III) tubulin immunostaining of PC12 cells on varied silk:GNP scaffolds under pulsed electrical stimulation (ES, 50 Hz frequency, 1 ms pulse width, and amplitudes of 100 and 300 mV/cm) demonstrates accelerated axonal growth on scaffolds exhibiting higher conductivity. This is supported by upregulated intracellular Ca2+ dynamics immediately after ES on the scaffolds with higher conductivity, subjected to a prolonged reduction period. The study showcases a sustainable reduction approach using l-Aa in combination with natural Bm silk fibroin to create a highly conductive, mechanically robust, and stable silk:GNP-based aligned fibrous scaffold. These scaffolds hold promise for functional regeneration in electrically excitable tissues such as nerves, cardiac tissue, and muscles.

Transcriptional profile features in patients with early and late preeclampsia

Aim: to assess the molecular mechanisms in developing various clinical phenotypes of preeclampsia (PE) by analyzing specific placental tissue transcriptome patterns. Materials and Methods. The prospective observational comparative study in parallel groups enrolled 43 pregnant women divided into 2 groups: main group – 23 pregnant women with diagnosed PE and control group – 20 apparently healthy women with uncomplicated pregnancy course, delivery and the postpartum period. To examine PE phenotypic features, the main group of pregnant women with PE was subsequently divided into 2 subgroups according to the date of pathology onset: early (n = 10) and late (n = 13) PE. Using the whole-genome next-generation sequencing (NGS), a comparative analysis of altered 18 microRNA level in placental tissue was carried out. Results. Pregnant women with early PE compared to the control group were characterized by significantly low expression level for hsa-miR-656-3p (p < 0.001), hsa-miR-323a-5p (p = 0.017), hsa-miR-519c-3p (p = 0.019), hsa-let-7i-5p (p = 0.019), hsa-miR-433-3p (p = 0.019), hsa-let-7g-5p (p = 0.030), hsa-miR-214-5p (p = 0.030), hsa-miR-27a-5p (p = 0.031), hsa-miR-339-5p (p = 0.041), hsa-miR-524-5p (p = 0.045), hsa-miR-1283 (p = 0.049) and high expression for hsa-miR-151a-5p (p = 0.007), hsa-miR-4521 (p = 0.018), hsa-miR-30d-5p (p = 0.026), hsa-miR-548l (p = 0.027), hsa-miR-133b (p = 0.034), hsa-miR-424-5p (p = 0.042), hsa-miR-211-5p (p = 0.049). Patients with late PE had significantly decreased expression for hsa-miR-656-3p (p = 0.050) andhsa-miR-574-3p (p = 0.017) as well as a significantly higher for hsa-miR-211-5p (p = 0.001) compared to the control group. Subgroup of women with early vs. late onset PE was characterized by significantly decreased expression level for hsa-miR-323-5p (p = 0.007) and overexpressed hsa-miR-30d-5p (p = 0.002), hsa-miR-5481 (p = 0.027). Conclusion. The noted multidirectional expression for some microRNAs in subgroups of PE patients confirms the validity for stratification of such pathology based on two distinct phenotypic manifestations (early and late forms) and indicates the existence of different pathophysiological vectors in PE formation.

Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver.

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.

B-esterases activities in several tissues of the marine fish: sea bass and hake, as potential biomarkers of bisphenol A derivatives

In the marine environment, a new threat linked to plastic pollution relates to plastic additives. This threat encompasses multiple chemical compound groups with a high bioaccumulation potential for these chemical mixtures. Hence, informative biomarkers are needed to indicate the effects of environmentally realistic mixtures of these additives. This study proposes an in vitro approach using tissue homogenates of two marine fish, the European sea bass and hake, which are both of interest in aquaculture and fisheries. The selected biomarkers are B-esterase activities comprising acetylcholinesterase (AChE) and carboxylesterases (CEs). The physiological role of AChE in brain and muscle is mainly neural transmission, while CEs participate in liver detoxification processes. However, B-esterases are also widely distributed in other tissues/organs, where their role is yet to be determined, but their inhibition may have undesired biological consequences. Here, we compared the interaction of the plastic additives, bisphenol A and some of its derivatives, like tetrabromobisphenol A (TBBPA), with B-esterase activities. We particularly focused not only on the robust and broadly distributed CE enzymes in brain, gonad, liver, kidney, and plasma tissues of two marine fish, but also on the use of two commercial substrates, p-nitrophenyl butyrate and α-naphthyl butyrate, tentatively representing two CE isoforms. The results evidenced specific species and tissue responses that could be due to a diverse isoform composition. They identified sea bass as better protected against neurotoxic exposures, at least in terms of B-esterase composition. The flame retardant TBBPA was the most reactive to B-esterases inhibition, although Bisphenol A bis (2,3-dihydroxy propyl) ether and Bisphenol F bis (3-chloro-2-hydroxypropyl) ether warrant further toxicology assessments.

Multifunctional scaffolds for biomedical applications: Crafting versatile solutions with polycaprolactone enriched by graphene oxide.

The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.

The Advancement and Obstacles in Improving the Stability of Nanocarriers for Precision Drug Delivery in the Field of Nanomedicine.

Nanocarriers have emerged as a promising class of nanoscale materials in the fields of drug delivery and biomedical applications. Their unique properties, such as high surface area- tovolume ratios and enhanced permeability and retention effects, enable targeted delivery of therapeutic agents to specific tissues or cells. However, the inherent instability of nanocarriers poses significant challenges to their successful application. This review highlights the importance of nanocarrier stability in biomedical applications and its impact on biocompatibility, targeted drug delivery, long shelf life, drug delivery performance, therapeutic efficacy, reduced side effects, prolonged circulation time, and targeted delivery. Enhancing nanocarrier stability requires careful design, engineering, and optimization of physical and chemical parameters. Various strategies and cutting-edge techniques employed to improve nanocarrier stability are explored, with a focus on their applications in drug delivery. By understanding the advances and challenges in nanocarrier stability, this review aims to contribute to the development and implementation of nanocarrier- based therapies in clinical settings, advancing the field of nanomedicine.

EDITORIAL: PIONEERING THE FUTURE OF HEALTHCARE THROUGH ADVANCES IN NOVEL DRUG DELIVERY SYSTEMS

With great delight and anticipation, I extend my heartfelt greetings to you as we commence a new venture with the latest release of the International Journal of Pharmacy and Integrated Health Sciences (IJPIHS). This issue is particularly noteworthy as it highlights the pivotal domains of Pharmaceutical Sciences, Clinical Pharmacy, and Drug Delivery Systems, demonstrating their significant influence on applications in healthcare.
 In the ever-evolving landscape of pharmaceuticals and healthcare, the quest for innovative drug delivery systems has emerged as a pivotal force, reshaping the dynamics of patient care and treatment outcomes. This editorial aims to shed light on the ground-breaking advancements in novel drug delivery systems, as we navigate the frontiers of the pharmaceutical industry in our pursuit of improved therapeutic efficacy and patient well-being. In recent years, the field of drug delivery has witnessed a paradigm shift, driven by a convergence of interdisciplinary research, technological breakthroughs, and a deep understanding of physiological processes. The International Journal of Pharmacy and Integrated Health Sciences is proud to contribute to this ongoing dialogue by showcasing the latest research and developments in novel drug delivery systems.
 One of the key challenges in traditional drug administration lies in achieving optimal drug concentrations at the target site while minimizing side effects. Novel drug delivery systems address this challenge by providing precise control over drug release kinetics, enhancing bioavailability, and enabling targeted delivery to specific tissues or cells. This not only maximizes therapeutic effects but also minimizes adverse reactions, thereby improving patient compliance and overall treatment outcomes.
 Nanotechnology has emerged as a frontrunner in this domain, offering unprecedented opportunities for designing advanced drug delivery platforms. Nanoparticles, liposomes, and micelles provide versatile carriers for drugs, allowing for controlled release and targeted delivery. These nanocarriers not only protect the drug from degradation but also facilitate its transport across biological barriers, opening new avenues for personalized medicine and tailored treatment strategies.
 As we delve into the articles featured in this issue of the International Journal of Pharmacy and Integrated Health Sciences, we invite our readers to explore the multifaceted world of novel drug delivery systems. From cutting-edge research on nanomedicine to the implementation of smart drug delivery devices, the diverse contributions in this journal underscore the transformative potential of these innovations in reshaping the future of healthcare. I want to convey my appreciation to the readers of IJPIHS for their ongoing support and active involvement with our journal. Your commitment to staying informed and exchanging knowledge fuels our relentless pursuit of excellence. Thank you for being part of this remarkable journey.

Radiation Therapy Technology Advances and Mitigation of Subsequent Neoplasms in Childhood Cancer Survivors

In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement. The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed. Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown. Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases.

Predicting Time-to-Healing from a Digital Wound Image: A Hybrid Neural Network and Decision Tree Approach Improves Performance

Despite the societal burden of chronic wounds and despite advances in image processing, automated image-based prediction of wound prognosis is not yet in routine clinical practice. While specific tissue types are known to be positive or negative prognostic indicators, image-based wound healing prediction systems that have been demonstrated to date do not (1) use information about the proportions of tissue types within the wound and (2) predict time-to-healing (most predict categorical clinical labels). In this work, we analyzed a unique dataset of time-series images of healing wounds from a controlled study in dogs, as well as human wound images that are annotated for the tissue type composition. In the context of a hybrid-learning approach (neural network segmentation and decision tree regression) for the image-based prediction of time-to-healing, we tested whether explicitly incorporating tissue type-derived features into the model would improve the accuracy for time-to-healing prediction versus not including such features. We tested four deep convolutional encoder–decoder neural network models for wound image segmentation and identified, in the context of both original wound images and an augmented wound image-set, that a SegNet-type network trained on an augmented image set has best segmentation performance. Furthermore, using three different regression algorithms, we evaluated models for predicting wound time-to-healing using features extracted from the four best-performing segmentation models. We found that XGBoost regression using features that are (i) extracted from a SegNet-type network and (ii) reduced using principal components analysis performed the best for time-to-healing prediction. We demonstrated that a neural network model can classify the regions of a wound image as one of four tissue types, and demonstrated that adding features derived from the superpixel classifier improves the performance for healing-time prediction.

Effect of Feeding Level on Growth and Slaughter Performance, and Allometric Growth of Tissues and Organs in Female Growing Saanen Dairy Goats.

This study aimed to investigate the effect of feeding level on the growth and slaughter performance, and allometric growth of tissues and organs in female growing dairy goats. The trial included 10-20 and 20-30 kg weight stages with 48 female goat kids. The 24 goat kids in each stage were divided into 8 blocks based on weight, with 3 kids per block. Then, three kids from each block were randomly assigned to one of the three treatments, namely ad libitum (AL100), 70% of ad libitum (AL70), or 40% of ad libitum (AL40). The slaughter trial was conducted when the AL100 kids reached the target weight of 20 or 30 kg. The results showed that the ADG and feed conversion rate showed a linear decline as the feed level decreased (p < 0.05). Compared with the AL70 and AL100 groups, the AL40 group exhibited lower shrunk body weight, empty body weight, hot carcass weight, net meat rate, carcass meat rate, and visceral fat weight (p < 0.05) in both stages. Moreover, the AL40 group showed lower weights for skin and mohair, blood, rumen, small intestine, large intestine, mammary gland, and uterus than the AL70 and AL100 groups (p < 0.05) in both stages. However, feeding level did not affect organ indices in the two stages (p > 0.05). The bone, skin and mohair were isometric (b ≈ 1), but the muscle, visceral fat, and most internal organs were positive (b > 1) in both stages. In conclusion, feeding level affects the growth and development of dairy goats, which vary depending on the body weight stage and specific tissues and organs.

CAM3.0: determining cell type composition and expression from bulk tissues with fully unsupervised deconvolution.

Complex tissues are dynamic ecosystems consisting of molecularly distinct yet interacting cell types. Computational deconvolution aims to dissect bulk tissue data into cell type compositions and cell-specific expressions. With few exceptions, most existing deconvolution tools exploit supervised approaches requiring various types of references that may be unreliable or even unavailable for specific tissue microenvironments. We previously developed a fully unsupervised deconvolution method-Convex Analysis of Mixtures (CAM), that enables estimation of cell type composition and expression from bulk tissues. We now introduce CAM3.0 tool that improves this framework with three new and highly efficient algorithms, namely, radius-fixed clustering to identify reliable markers, linear programming to detect an initial scatter simplex, and a smart floating search for the optimum latent variable model. The comparative experimental results obtained from both realistic simulations and case studies show that the CAM3.0 tool can help biologists more accurately identify known or novel cell markers, determine cell proportions, and estimate cell-specific expressions, complementing the existing tools particularly when study- or datatype-specific references are unreliable or unavailable. The open-source R Scripts of CAM3.0 is freely available at https://github.com/ChiungTingWu/CAM3/(https://github.com/Bioconductor/Contributions/issues/3205). A user's guide and a vignette are provided.

Loss of function in somatostatin receptor 5 has no impact on the growth of medaka fish due to compensation by the other paralogs

Somatic growth in vertebrates is regulated endocrinologically by the somatotropic axis, headed by the growth hormone (GH) and the insulin growth factor-I (IGF-I). Somatostatin (Sst), a peptide hormone synthesized in the hypothalamus, modulates GH actions through its receptors (Sstr). Four Sstr subtypes (Sstr 1–3 and 5) have been identified in teleosts. However, little is known about whether they have a specific function or tissue expression. The aim of this study was to determine the role of sstr2 and sstr5 in the growth of the medaka (Oryzias latipes). The assessed expression pattern across diverse tissues highlighted greater prevalence of sstr1 and sstr3 in brain, intestine and muscle than in pituitary or liver. The expression of sstr2 was high in all the tissues tested, while sstr5 was predominantly expressed in the pituitary gland. A CRISPR/Cas9 sstr5 mutant with loss of function (sstr5-/-) was produced. Assessment of sstr5-/- indicated no significant difference with the wild type regarding growth parameters such as standard length, body depth, or peduncle depth. Furthermore, the functional loss of sstr5 had no impact on the response to a nutritional challenge. The fact that several sstr subtypes were upregulated in different tissues in sstr5-/- medaka suggests that in the mutant fish, there may be a compensatory effect on the different tissues, predominantly by sstr1 in the liver, brain and pituitary, with sstr2 being upregulated in pituitary and liver, and sstr3 only presenting differential expression in the brain. Analysis of the sstr subtype and the sstr5-/- fish showed that sstr5 was not the only somatostatin receptor responsible for Sst-mediated Gh regulation.