Current Challenges Research Articles

Completion of multidose vaccine series in early childhood: current challenges and opportunities.

Completion of all doses in multidose vaccine series provides optimal protection against preventable infectious diseases. In this review, we describe clinical and public health implications of multidose vaccine series noncompletion, including current challenges to ensuring children receive all recommended vaccinations. We then highlight actionable steps toward achieving early childhood immunization goals. Although coverage levels are high for most early childhood vaccinations, rates of completion are lower for vaccinations that require multiple doses. Recent research has shown that lower family socioeconomic status, a lack of health insurance coverage, having multiple children in the household, and moving across state lines are associated with children failing to complete multidose vaccine series. These findings provide contextual evidence to support that practical challenges to accessing immunization services are impediments to completion of multidose series. Strategies, including reminder/recall, use of centralized immunization information systems, and clinician prompts, have been shown to increase immunization rates. Re-investing in these effective interventions and modernizing the public health infrastructure can facilitate multidose vaccine series completion. Completion of multidose vaccine series is a challenge for immunization service delivery. Increased efforts are needed to address remaining barriers and improve vaccination coverage in the United States.

Developments and Trends of Nanotechnology Application in Sepsis: A Comprehensive Review Based on Knowledge Visualization Analysis.

Sepsis, a common life-threatening clinical condition, continues to have high morbidity and mortality rates, despite advancements in management. In response, significant research efforts have been directed toward developing effective strategies. Within this scope, nanotechnology has emerged as a particularly promising field, attracting significant interest for its potential to enhance disease diagnosis and treatment. While several reviews have highlighted the use of nanoparticles in sepsis, comprehensive studies that summarize and analyze the hotspots and research trends are lacking. To identify and further promote the development of nanotechnology in sepsis, a bibliometric analysis was conducted on the relevant literature, assessing research trends and hotspots in the application of nanomaterials for sepsis. Next, a comprehensive review of the subjectively recognized research hotspots in sepsis, including nanotechnology-enhanced biosensors and nanoscale imaging for sepsis diagnostics, and nanoplatforms designed for antimicrobial, immunomodulatory, and detoxification strategies in sepsis therapy, is elucidated, while the potential side effects and toxicity risks of these nanomaterials were discussed. Particular attention is given to biomimetic nanoparticles, which mimic the biological functions of source cells like erythrocytes, immune cells, and platelets to evade immune responses and effectively deliver therapeutic agents, demonstrating substantial translational potential. Finally, current challenges and future perspectives of nanotechnology applications in sepsis with a view to maximizing their great potential in the research of translational medicine are also discussed.

Electrochemical-induced hydrofunctionalizations of alkenes and alkynes

The hydrofunctionalizations of readily available alkenes and alkynes are one of the most effective and useful routes to afford diverse value-added compounds. Although traditional hydrofunctionalization strategies catalyzed by metal catalysts present convenient approaches, they are also accompanied by resource consumption and environmental crisis. Electrosynthesis, as a renewable and sustainable technology, has become a cost- and atom-efficient and useful synthetic route. In this review, the electrochemical-induced hydrofunctionalizations of alkenes and alkynes are summarized and presented. In each section, the electrochemical synthetic strategy to access hydrogenation and other hydrofunctionalization (hydroboration, hydrosilylation, hydroalkylation, hydroalkoxylation, hydrocyanation, hydrocarboxylation, etc. ) products are elaborated in detail separately. Finally, the current challenges and prospects for electrochemical hydrofunctionalizations of unsaturated carbon‒carbon (C‒C) bonds are also discussed briefly.

Public access defibrillation programs: Progetto Vita, current legal aspects and challenges for the future

Out-of-hospital cardiac arrest (OHCA) represents a significant healthcare issue that is often underestimated. OHCA predominantly affects the general population, with staggering numbers: 400 000 cases annually in Europe and 350 000 in the United States, contributing to 50% of cardiovascular-related deaths. The vast majority of OHCA cases begin with a shockable rhythm, making effective treatment possible through early defibrillation, even by non-medical personnel using automated external defibrillators (AEDs). Despite the availability of such devices, survival from OHCA remains below 10%, with no substantial improvements over the last 25 years. Public access defibrillation programs, which reduce response times with AEDs, have demonstrated a significant increase in survival chances for OHCA victims. Particularly, the "Progetto Vita" in Piacenza is an emblematic example of early defibrillation in Europe, tripling survival rates in OHCA patients treated by laypersons compared to patients treated with the traditional system. This experience contributed to the approval of Law 116, dated August 4, 2021, in Italy, aimed at promoting the distribution and use of AEDs in sports facilities, public venues, transportation, and public services. The law also emphasizes that AEDs can be used without the need for specific training, thus promoting wider usage. In this article, we will briefly examine the epidemiology of OHCA and delve into the organizational model of the "Progetto Vita", which aligns with the principles of Law 116/2021. The goal is to provide some insights into organizational aspects that could facilitate the nationwide expansion of early defibrillation programs in the near future.

Unveiling the potential of Daldinia eschscholtzii MFLUCC 19-0629 through bioactivity and bioinformatics studies for enhanced sustainable agriculture production

Endophytic fungi constitute a rich source of secondary metabolites that can be manipulated to produce desirable novel analogs for combating current agricultural challenges for crop production, especially controlling plant disease. The endophytic fungus Daldinia eschscholtzii MFLUCC 19-0629, was newly isolated from tropical ancient plants, Oncosperma sp., and displays a broad-spectrum of antifungal and antibacterial activities against several plant pathogens including Ralstonia solanacearum, Fusarium oxysporum, Colletotrichum gloeosporioides, Colletotrichum acutatum, Stagonosporopsis cucurbitacearum, Corynespora cassiicola and Stemphylium spp. A high-quality genome sequence was obtained using Oxford nanopore technology, the accuracy and length of reads resulting in no need for Illumina or other sequencing techniques, for D. eschscholtzii MFLUCC 19-0629, resulting in a genome size of 37.56 Mb assembled over 11 contigs of significant size, likely to be at the chromosomal level. Bioinformatics analysis revealed that this strain is biosynthetically talented encoding 67 predicted biosynthetic gene clusters (BGCs). Only eight of the 67 BGCs matched or demonstrated high similarity to previously characterized BGCs linked to the production of known secondary metabolites. The high number of predicted unknown BGCs makes this strain a promising source of novel natural products. The discovery that D. eschscholtzii MFLUCC 19-0629 has a broad spectrum of antimicrobial activity against seven major plant pathogenic microorganisms relevant to crop production and its complete genome sequence carries immense importance in the advancement of novel microbial biocontrol agents (MBCAs). This also unveils the prospect of uncovering new compounds that could be utilized for sustainable agriculture and pharmaceutical purposes.

A Review of Current Trends, Techniques, and Challenges in Large Language Models (LLMs)

Natural language processing (NLP) has significantly transformed in the last decade, especially in the field of language modeling. Large language models (LLMs) have achieved SOTA performances on natural language understanding (NLU) and natural language generation (NLG) tasks by learning language representation in self-supervised ways. This paper provides a comprehensive survey to capture the progression of advances in language models. In this paper, we examine the different aspects of language models, which started with a few million parameters but have reached the size of a trillion in a very short time. We also look at how these LLMs transitioned from task-specific to task-independent to task-and-language-independent architectures. This paper extensively discusses different pretraining objectives, benchmarks, and transfer learning methods used in LLMs. It also examines different finetuning and in-context learning techniques used in downstream tasks. Moreover, it explores how LLMs can perform well across many domains and datasets if sufficiently trained on a large and diverse dataset. Next, it discusses how, over time, the availability of cheap computational power and large datasets have improved LLM’s capabilities and raised new challenges. As part of our study, we also inspect LLMs from the perspective of scalability to see how their performance is affected by the model’s depth, width, and data size. Lastly, we provide an empirical comparison of existing trends and techniques and a comprehensive analysis of where the field of LLM currently stands.

Advancing high‐performance one‐dimensional Si/carbon anodes: Current status and challenges

AbstractSilicon (Si) anodes, known for their high capacity, confront obstacles such as volume expansion, the solid–electrolyte interface (SEI) formation, and limited cyclability, driving ongoing research for innovative solutions to enhance their performance in next‐generation lithium‐ion batteries (LIBs). This comprehensive review explores the forefront of one‐dimensional (1D) Si/carbon anodes for high‐performance LIBs. This review delves into cutting‐edge strategies for fabricating 1D Si/carbon structures, such as nanowires, nanotubes, and nanofibers, highlighting their advantages in mitigating volume expansion, enhancing electron/ion transport, and bolstering cycling stability. The review showcases remarkable achievements in 1D Si/carbon anode performance, including exceptional capacity retention, high‐rate capability, and prolonged cycle life. Challenges regarding scalability, cost‐effectiveness, and long‐term stability are addressed, providing insights into the path to commercialization. Additionally, future directions and potential breakthroughs are outlined, guiding researchers and industries toward harnessing the potential of 1D Si/carbon anodes in revolutionizing energy storage.

Review of the policies and development programs for renewable energy in Malaysia: Progress, achievements and challenges

In 2022, Malaysia was ranked 28th worldwide in terms of its energy oil consumption. Energy consumption in Malaysia has been predominantly reliant on natural gas and coal in both the past and present. Oil and gas in Malaysia are predicted to be depleted in 14 years due to the high energy consumption, especially from petroleum sources. Thus, the Malaysian government aims to expand renewable energy (RE) in the country's energy mix as an alternative source of energy. As of 2022, Malaysia has generated roughly 2% of its electricity from various renewable sources, which is still far from the initial target of reaching 20% RE penetration by 2030. However, since 2017, RE has started to contribute to energy mix generation. Several policies, including an act, have been implemented in Malaysia to achieve the target in RE, but many challenges and difficulties have hindered the progress. Thus, the present study explored the current status and challenges for RE in Malaysia and discussed the effectiveness of the available energy policies and programs. The outcomes are potentially valuable to Malaysian policymakers, industries and researchers to improve their current practices for achieving the initial national RE target by 2030 as well as to move forward towards net zero emissions by 2050. This study provides a crucial roadmap for Malaysia to achieve its RE objectives and contribute significantly to the international transition towards a more environmentally friendly and sustainable future.

Chitosan-based Nanomedicine in the Management of Age-related Macular Degeneration: A Review

Abstract: Age-related macular degeneration (AMD) is a leading cause of permanent blindness globally. Due to the various obstacles, highly invasive intravitreal (IVT) injections are the prima-ry method used to deliver medications to the tissues of the posterior eye. An utmost patient-friendly topical ocular delivery approach has been extensively researched in recent years. Muco-adhesive compositions extend precorneal residence time while reducing precorneal clearance. They increase the likelihood of adhesion to corneal and conjunctival surfaces and, as a result, al-low for enhanced delivery to the posterior eye segment. Due to its remarkable mucoadhesive characteristics, chitosan (CS) has undergone the most extensive research of any mucoadhesive polymer. Drug delivery to the front and back of the eye is still difficult. The pharmaceutical in-dustry has shown greater interest in drug delivery systems (DDSs) based on nanotechnology (NT) in recent years, particularly those made from natural polymers like chitosan, alginate, etc. Be-cause of their incredible adaptability, higher biological effects, and favourable physicochemical properties, CS-oriented nanomaterials (NMs) are explored by researchers as prospective nanocar-riers. CS are the right substrates to develop pharmaceutical products, such as hydrogels, nanopar-ticles (NP), microparticles, and nanofibers, whether used alone or in composite form. CS-based nanocarriers deliver medicine, such as peptides, growth factors, vaccines, and genetic materials in regulated and targeted form. This review highlights current developments and challenges in chi-tosan-mediated nano therapies associated with AMD.

Investigation of Current Practices and Challenges of Stakeholder Management Process in Construction Projects

In the construction industry, stakeholder management is essential for project success because it entailslocating, evaluating, and proactively interactingwith people or organizations that have the potential to have a substantial impact on project. Due to the involvement of multiple parties, including clients, contractors, subcontractors, regulatory bodies, local communities, and environmental organizations, the construction business is intrinsically complicated. Achieving project objectives, minimizing conflicts, and addressing a variety of interests all depend on effective stakeholder management. In this research, the various challenges faced by the stakeholders are identified. Alongside, the current practices followed by the stakeholders in the construction projects are explored. Based on that, the factors affecting stakeholders’ management on project performance are investigated. This research aims at identifying the most critical factors affecting the stakeholder’s performance across project success through a conceptual framework. This paper explains the direct impact made in project cycle due to stakeholder performance and major problems faced by the construction industries due to improper allocation of stakeholders. A review of earlier stakeholder management research is conducted to accomplish this goal. Keywords: Construction, stakeholders, performance, framework

Unlocking the potential of cybersecurity behavior in the metaverse: Overview, opportunities, challenges, and future research agendas

The metaverse, often referred to as the next stage of the Internet, is a virtual space that utilizes advanced technologies, such as augmented reality, virtual reality, and mixed reality, to enable real-time engagement and experiences beyond what can be achieved in reality. Cybersecurity behavior in the metaverse refers to the actions taken by individuals and organizations to protect themselves and their information from various cyber threats in virtual reality environments by implementing various cybersecurity measures. Research on cybersecurity behavior in the metaverse is still limited. This study offers an overview of cybersecurity behavior in the metaverse and identifies a range of potential opportunities. It also discusses the current and prospective challenges and suggests large-scale research agendas that can be examined in future research. The research agendas encompass extensive subject areas, such as security of the metaverse, influential factors, human behavior in the metaverse, virtual identity and access management, privacy, legal, and ethical issues, and cybersecurity education and awareness. This study offers a crucial and timely insight into cybersecurity practices in the metaverse, considering the advancement of metaverse technology.

A Review on Speech-to-Text

The current era represents the global apex of groundbreaking advances in artificial intelligence (AI) technology, especially in the field of speech-to-text (STT).This review article focuses on the development of human skills through smooth, natural language interaction between people and robots, providing a thorough overview and exploration of the impressive advancements made in recent years. The study outlines a model intended to reinvent human-computer interaction, highlighting its ability to translate spoken language into text and carry out commands via a conversational, dynamic interface. Real-world applications examine neural network designs, deep learning, natural language processing, and multimodal approaches;Python acts as the engine of execution, utilizing large-scale libraries like pyttsx3 and speech recognition. The model's development is highlighted by the investigation of methods, such as neural network topologies, which handle issues with various speech patterns, accents, and background noise. In the current AI scene, the study wants to contribute to existing discussions on the revolutionary influence of STT technology on human- computer interaction, despite current challenges including processing nuanced language and minimizing the impact of background noise on recognition accuracy. Keywords—Speech-to-Text(STT), Natural language processing, Python-driven execution and libraries, Multimodal Approaches, Deep Learning, Recognition accuracy, Human- computer Interaction, Desktop Voice Assistant

A Tale of a Trail on How It Takes 5 Days of Kawasaki Disease to Initiate Coronary Artery Injury and Change the Lives of Children.

Many articles written on Kawasaki disease explain the disease and the history of an acute inflammatory dysregulation that typically affects preschool children and does not spare older ones. Six decades have passed since the discovery of the disease in Japan, yet there are parts of the world where the disease passes unacknowledged, diagnosis is delayed, or basic treatments are not readily available. The burden of Kawasaki disease is on every health-care provider who attends to children's health. It takes 5 days for the disease to initiate coronary artery injury in a child's heart, compared to 5 decades of lifetime atherosclerosis. Challenges facing patients, families, and physicians may not be overcome unless we advocate for the disease recognition and seek support for affordable, timely treatment, impactful research, and dissemination of knowledge. The purpose of this review is to provide a comprehensive review of the history of Kawasaki disease and how it has affected children's health worldwide over the last 6 decades. The review also raises current challenges facing the fight against Kawasaki disease. In an effort to bring Kawasaki disease advocates together in a landing zone, an internet hub for Kawasaki disease experts and enthusiasts has been created: the International Kawasaki Disease Society (presently a concept idea) and a dedicated website, www.ikds-org.

Carbon dots based fluorescence sensor for P-nitrophenol

P-nitrophenol (p-NP) is a hazardous chemical contaminant that can enter the body and cause health issues. The current sensor for detecting p-NP is complex to operate and cannot be used on-site. Therefore, it is essential to develop a highly sensitive and selective material for the determination of p-NP in real-time, such as a fluorescence sensor. Carbon dots (CDs) possess exceptional photoluminescence (PL) properties, making them promising for sensing applications. This review presents the recent advancement, synthesis strategies, and optical properties of CDs fluorescence sensors. Additionally, we enlighten the application and current challenges of the use of CDs as a sensor for detecting p-NP.

Intestinal organoid modeling: bridging the gap from experimental model to clinical translation.

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name "mini-intestines". Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

Where Are All the Specialists? Current Challenges of Integrating Specialty Care Into Population-Based Total Cost of Care Payment Models.

The Centers for Medicare & Medicaid Services Innovation Center (CMMI) has set the goal for 100% of traditional Medicare beneficiaries to be part of an accountable care relationship by 2030. Lack of meaningful financial incentives, intolerable or unpredictable risk, infrastructure costs, patient engagement, voluntary participation, and operational complexity have been noted by the provider and health care delivery community as barriers to participation or reasons for exiting programs. In addition, most piloted and implemented population-based total cost of care (PB-TCOC) payment models have focused on the role of the primary care physician being the accountability (that is, attributable) leader of a patient's multifaceted care team as well as acting as the mayor of the "medical neighborhood," leaving the role of specialty care physicians undefined. Successful provider specialist integration into PB-TCOC models includes meaningful participation of specialists in achieving whole-person, high-value care where all providers are financially motivated to participate; there is unambiguous prospective attribution and clearly defined accountability for each participating party throughout the care journey or episode; there is a known care attribution transition accountability plan; there is actionable, transparent, and timely data available with appropriate data development and basic analytic costs covered; and there is advanced payment to the accountable person or entity for management of the care episode that is part of a longitudinal care plan. Payment models should be created to address the 7 challenges raised here if specialists are to be incented to join TCOC models that achieve CMMI's goal.

JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target.

Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling.

Exploring the intricate cross-talk between clonal expansion and the bone marrow niche

Haematopoietic stem cells (HSCs) reside within an intricate network of cells in the bone marrow (BM) niche. HSC crosstalk with niche compartments influences lineage determination and blood cell production, while independent niche interactions are essential for the maintenance of HSC quiescence. How different niche components influence the genetic diversity of HSCs represents an expanding field of investigation. As such, we will summarise the current knowledge of the contribution to the Darwinian evolution of mutant HSCs of both haematopoietic and non-haematopoietic cells residing in the BM. In this review, we will disentangle how somatic evolution associates with the niche at two stages: from (1) the stage of preleukaemic HSC expansion and clonal haematopoiesis (CH) to (2) leukaemia-initiating cells (LICs) and the development of myeloid malignancies with acute myeloid leukaemia (AML) being the most prevalent. We will finally describe current challenges such as limitations in models used in the field or the difficulty in studying specific genetic clones in isolation.

Immune interface interference vaccines: An evolution-informed approach to anti-bacterial vaccine design.

Developing protein-based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti-bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high-throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, 'immune interface interference' (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H-binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein-based vaccines to prevent bacterial infections.

Engineering models of head and neck and oral cancers on-a-chip.

Head and neck cancers (HNCs) rank as the sixth most common cancer globally and result in over 450 000 deaths annually. Despite considerable advancements in diagnostics and treatment, the 5-year survival rate for most types of HNCs remains below 50%. Poor prognoses are often attributed to tumor heterogeneity, drug resistance, and immunosuppression. These characteristics are difficult to replicate using in vitro or in vivo models, culminating in few effective approaches for early detection and therapeutic drug development. Organs-on-a-chip offer a promising avenue for studying HNCs, serving as microphysiological models that closely recapitulate the complexities of biological tissues within highly controllable microfluidic platforms. Such systems have gained interest as advanced experimental tools to investigate human pathophysiology and assess therapeutic efficacy, providing a deeper understanding of cancer pathophysiology. This review outlines current challenges and opportunities in replicating HNCs within microphysiological systems, focusing on mimicking the soft, glandular, and hard tissues of the head and neck. We further delve into the major applications of organ-on-a-chip models for HNCs, including fundamental research, drug discovery, translational approaches, and personalized medicine. This review emphasizes the integration of organs-on-a-chip into the repertoire of biological model systems available to researchers. This integration enables the exploration of unique aspects of HNCs, thereby accelerating discoveries with the potential to improve outcomes for HNC patients.