Comparing The Effects of Compression Contrast Therapy and Dry Needling on Muscle Functionality, Pressure Pain Threshold, and Perfusion after Isometric Fatigue in Forearm Muscles of Combat Sports Athletes: A Single-Blind Randomized Controlled Trial.

The aim of this study was to compare the acute effects of compression contrast therapy (CT) and dry needling therapy (DN) on muscle tension (MT), muscle strength (Fmax), pressure pain threshold (PPT), and perfusion (PU) following fatigue of forearm muscles (e.g., flexor carpi radialis) in combat sports athletes. A single-blind randomized controlled trial was employed. Participants first underwent muscle fatigue induction, which involved sustaining an isometric handgrip at 60% of their maximum voluntary contraction in 5-second cycles. This was followed by exposure to one of the regenerative therapies. Forty-five participants were randomly assigned to one of three groups: CT/DN (n = 15), CT/ShDN (n = 15), and ShCT/DN (n = 15). The sham condition (Sh) involved a simulated version of the technique. Measurements were taken at four time points: (i) at rest; (ii) immediately after exercise that led to a state of fatigue; (iii) 5 minutes after therapy (PostTh5min); and (iv) 24 hours after therapy (PostTh24h). Each participant was exposed to one experimental condition and one control condition, thereby undergoing evaluation in two sessions. Significant differences between groups were found in MT during the PostTh5min (p = 0.005), as well as in PU during the PostTh5min (p < 0.001) and PU during the PostTh24h (p < 0.001). All groups showed significant improvements at 5 minutes post-therapy compared to immediately post-muscle fatigue. As conclusions, CT/DN seems to be significantly better for enhancing MT and PU after 5 minutes of muscle fatigue induction. Using either CT, DN, or both combined is recommended to enhance the recovery of muscle functionality and properties, favoring recovery and potentially speeding up performance enhancement.

Cognitive Behavioral Therapy and Mindfulness-Based Cognitive Therapy for Depressive Disorders: Enhancing Access and Tailoring Interventions in Diverse Settings.

Depressive disorders are an enormous societal burden given their high prevalence and impact on all facets of being human (e.g., relationships, emotions, motivation). There is a variety of evidence-based psychological treatments, with cognitive behavioral therapy (CBT) being the gold standard for major depression. Research has shown that mindfulness-based interventions (MBIs) such as mindfulness-based cognitive therapy (MBCT) are an effective relapse prevention and treatment for depression and that MBIs can be integrated in individual therapy. Furthermore, various delivery modes (e.g., digital-delivered therapy) and settings are offered to best meet different needs and improve accessibility: Evidence suggests that therapist-guided digital CBT, blended therapy, and, to some degree, digitalized MBIs may be an efficacious supplement to traditional face-to-face therapy. This chapter provides an overview of the principles and evidence base for CBT and MBCT as well as different delivery modes for depressive disorders in adults. Finally, chances and challenges of integration are discussed as implications for practice, as well as recommendations and ideas for future research.

The New Emerging Treatment Choice for Major Depressive Disorders: Digital Therapeutics.

The chapter provides an in-depth analysis of digital therapeutics (DTx) as a revolutionary approach to managing major depressive disorder (MDD). It discusses the evolution and definition of DTx, their application across various medical fields, regulatory considerations, and their benefits and limitations. This chapter extensively covers DTx for MDD, including smartphone applications, virtual reality interventions, cognitive-behavioral therapy (CBT) platforms, artificial intelligence (AI) and chatbot therapies, biofeedback, wearable technologies, and serious games. It evaluates the effectiveness of these digital interventions, comparing them with traditional treatments and examining patient perspectives, compliance, and engagement. The integration of DTx into clinical practice is also explored, along with the challenges and barriers to their adoption, such as technological limitations, data privacy concerns, ethical considerations, reimbursement issues, and the need for improved digital literacy. This chapter concludes by looking at the future direction of DTx in mental healthcare, emphasizing the need for personalized treatment plans, integration with emerging modalities, and the expansion of access to these innovative solutions globally.

Revolutionizing Ophthalmic Care: A Review of Ocular Hydrogels from Pathologies to Therapeutic Applications.

PURPOSE: This comprehensive review is designed to elucidate the transformative role and multifaceted applications of ocular hydrogels in contemporary ophthalmic therapeutic strategies, with a particular emphasis on their capability to revolutionize drug delivery mechanisms and optimize patient outcomes. METHODS: A systematic and structured methodology is employed, initiating with a succinct exploration of prevalent ocular pathologies and delineating the corresponding therapeutic agents. This serves as a precursor for an extensive examination of the diverse methodologies and fabrication techniques integral to the design, development, and application of hydrogels specifically tailored for ophthalmic pharmaceutical delivery. The review further scrutinizes the pivotal manufacturing processes that significantly influence hydrogel efficacy and delves into an analysis of the current spectrum of hydrogel-centric ocular formulations. RESULTS: The review yields illuminating insights into the escalating prominence of ocular hydrogels within the medical community, substantiated by a plethora of ongoing clinical investigations. It reveals the dynamic and perpetually evolving nature of hydrogel research and underscores the extensive applicability and intricate progression of transposing biologics-loaded hydrogels from theoretical frameworks to practical clinical applications. CONCLUSIONS: This review accentuates the immense potential and promising future of ocular hydrogels in the realm of ophthalmic care. It not only serves as a comprehensive guide but also as a catalyst for recognizing the transformative potential of hydrogels in augmenting drug delivery mechanisms and enhancing patient outcomes. Furthermore, it draws attention to the inherent challenges and considerations that necessitate careful navigation by researchers and clinicians in this progressive field.

Psychological aspects of vestibular disorders: a national survey of clinical practice.

OBJECTIVE: This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation. METHOD: An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice. RESULTS: Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise. CONCLUSION: Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.

Complement-targeted therapeutics: Are we there yet, or just getting started?

Therapeutic interventions in the complement system, a key immune-inflammatory mediator and contributor to a broad range of clinical conditions, have long been considered important yet challenging or even unfeasible to achieve. Almost 20 years ago, a spark was lit demonstrating the clinical and commercial viability of complement-targeted therapies. Since then, the field has experienced an impressive expansion of targeted indications and available treatment modalities. Currently, a dozen distinct complement-specific therapeutics covering several intervention points are available in the clinic, benefiting patients suffering from eight disorders, not counting numerous clinical trials and off-label uses. Observing this rapid rise of complement-targeted therapy from obscurity to mainstream with amazement, one might ask whether the peak of this development has now been reached or whether the field will continue marching on to new heights. This review looks at the milestones of complement drug discovery and development achieved so far, surveys the currently approved drug entities and indications, and ventures a glimpse into the future advancements yet to come.

A Smart Water Bottle and Companion App (HidrateSpark 3) to Improve Bladder-Filling Compliance in Patients With Prostate Cancer Receiving Radiotherapy: Nonrandomized Trial of Feasibility and Acceptability.

BACKGROUND: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE). OBJECTIVE: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE. METHODS: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both pieces alert the patient to empty his bladder and drink a personalized volume goal, based on simulation bladder volume, 1.25 hours before his scheduled RT. Patients were trained to adjust their volume goal and notification times to achieve comfortably full bladders. The primary end point was met if qualitative (QLC) and quantitative compliance (QNC) were >80%. For QLC, patients were asked if they prepared their bladders before daily RT. QNC was met if bladder volumes on daily cone-beam tomography were >75% of the simulation's volume. The Service User Technology Acceptability Questionnaire (SUTAQ) was given in person pre- and post-SBI. Additional acceptability and engagement end points were met if >3 out of 5 across 4 domains on the SUTAQ and >80% (15/18) of patients used the device >50% of the time, respectively. Finally, the impact of SBI on PV and TE was measured by time spent in a clinic and on the linear accelerator (linac), respectively, and contrasted with matched controls. RESULTS: QLC was 100% in 375 out of 398 (94.2%) total treatments, while QNC was 88.9% in 341 out of 398 (85.7%) total treatments. Of a total score of 5, patients scored 4.33 on privacy concerns, 4 on belief in benefits, 4.56 on satisfaction, and 4.24 on usability via SUTAQ. Further, 83% (15/18) of patients used the SBI on >50% of treatments. Patients in the intervention arm spent less time in a clinic (53.24, SEM 1.71 minutes) compared to the control (75.01, SEM 2.26 minutes) group (P<.001). Similarly, the intervention arm spent less time on the linac (10.67, SEM 0.40 minutes) compared to the control (14.19, SEM 0.32 minutes) group (P<.001). CONCLUSIONS: This digital intervention trial showed high rates of bladder-filling compliance and engagement. High patient value and TE were feasibly quantified by shortened clinic times and linac usage, respectively. Future studies are needed to evaluate clinical outcomes, patient experience, and cost-benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT04946214; https://www.clinicaltrials.gov/study/NCT04946214.

A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia-Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a common and highly fatal hyperinflammatory syndrome characterized by the aberrant activation of macrophages. To date, there is a lack of targeted therapies for HLH. It is validated that macrophages in HLH efficiently phagocytose anti-CD41-platelets (anti-CD41-PLTs) from immune thrombocytopenia (ITP) patients in previous research. Hence, the pathological mechanisms of ITP are mimicked and anti-CD41-PLTs are utilized to load the macrophage-toxic drug VP16 to construct macrophage-targetable engineered platelets anti-CD41-PLT-VP16, which is a novel targeted therapy against HLH. Both in vitro and in vivo studies demonstrate that anti-CD41-PLT-VP16 has excellent targeting and pro-macrophage apoptotic effects. In HLH model mice, anti-CD41-PLT-VP16 prevents hemophagocytosis and inhibits the cytokine storm. Mechanistic studies reveal that anti-CD41-PLT-VP16 increases the cytotoxicity of VP16, facilitating precise intervention in macrophages. Furthermore, it operates as a strategic "besieger" in diminishing hyperinflammation syndrome, which can indirectly prevent the abnormal activation of T cells and NK cells and reduce the Ab-dependent cell-mediated cytotoxicity effect. The first platelet-based clinical trial is ongoing. The results show that after treatment with anti-CD41-PLT-VP16, HLH patients have a threefold increase in the overall response rate compared to patients receiving conventional chemotherapy. In conclusion, anti-CD41-PLT-VP16 provides a general insight into hyperinflammation syndrome and offers a novel clinical therapeutic strategy for HLH.

Stable excess mortality in a multiple sclerosis cohort diagnosed 1970-2010.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is associated with excess mortality. The use of disease-modifying treatments (DMTs) has recently been associated with survival benefits. METHODS: A regional MS database was linked with national registries. People with MS (pwMS) diagnosed in 1971-2010 were included and followed up until the end of the year 2019. Five matched controls were acquired for every person with MS. DMTs included in the analyses were interferon and glatiramer acetate. RESULTS: Median follow-up time of the 1795 pwMS was 20.0 years (range 0.1-48.7 years). Survival did not differ between decades of diagnosis (p = 0.20). Amongst pwMS, male sex (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI] 1.41-2.06), higher age at diagnosis (aHR 1.83; 95% CI 1.65-2.03 per 10-year increment) and primary progressive disease course (aHR 1.29; 95% CI 1.04-1.60) were independently associated with poorer survival. DMT use was associated with better survival (p < 0.0001) and better survival during follow-up (aHR 0.56; 95% CI 0.38-0.81). Compared to matched controls, median life expectancy was 8-9 years shorter in pwMS with survival diverging from controls during the first decade after diagnosis, more clearly in men than women. CONCLUSION: Despite DMT use being associated with better survival, relative life expectancy of pwMS did not change over five decades in Western Finland. Male sex was an independent risk factor for death amongst pwMS, but excess mortality was higher in women. More work and methods are needed to improve survival in pwMS.

Redefining drug therapy: innovative approaches using catalytic compartments.

INTRODUCTION: Rapid excretion of drug derivatives often results in short drug half-lives, necessitating frequent administrations. Catalytic compartments, also known as nano- and micro-reactors, offer a solution by providing confined environments for in situ production of therapeutic agents. Inspired by natural compartments, polymer-based catalytic compartments have been developed to improve reaction efficiency and enable site-specific therapeutic applications. AREAS COVERED: Polymer-based compartments provide stability, permeability control, and responsiveness to stimuli, making them ideal for generating localized compounds/signals. These sophisticated systems, engineered to carry active compounds and enable selective molecular release, represent a significant advancement in pharmaceutical research. They mimic cellular functions, creating controlled catalytic environments for bio-relevant processes. This review explores the latest advancements in synthetic catalytic compartments, focusing on design approaches, building blocks, active molecules, and key bio-applications. EXPERT OPINION: Catalytic compartments hold transformative potential in precision medicine by improving therapeutic outcomes through precise, on-site production of therapeutic agents. While promising, challenges like scalable manufacturing, biodegradability, and regulatory hurdles must be addressed to realize their full potential. Addressing these will be crucial for their successful application in healthcare.

Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors.

Fibroblast activation protein (FAP) is abundantly expressed in the stroma of most human solid tumors. Clinical-stage radiolabeled FAP ligands are increasingly used as tools for the detection of various cancer lesions. To unleash the full therapeutic potential of FAP-targeting agents, ligands need to remain at the tumor site for several days after administration. We recently described the discovery of OncoFAP, a high-affinity small organic ligand of FAP with a rapid accumulation in tumors and low uptake in healthy tissues in cancer patients. Trimerization of OncoFAP provided a derivative (named TriOncoFAP, or OncoFAP-23) with improved FAP affinity. In this work, we evaluated the tissue biodistribution profile and the therapeutic performance of OncoFAP-23 in tumor-bearing mice. Methods: OncoFAP-23 was radiolabeled with the theranostic radionuclide 177Lu. Preclinical experiments were conducted on mice bearing SK-RC-52.hFAP (BALB/c nude mice) or CT-26.hFAP (BALB/c mice) tumors. 177Lu-OncoFAP and 177Lu-FAP-2286 were included in the biodistribution study as controls. Toxicologic evaluation was performed on Wistar rats and CD1 mice by injecting high doses of OncoFAP-23 or its cold-labeled counterpart, respectively. Results: 177Lu-OncoFAP-23 emerged for its best-in-class biodistribution profile, high and prolonged tumor uptake (i.e., ∼16 percentage injected dose/g at 96 h), and low accumulation in healthy organs, which correlates well with its potent single-agent anticancer activity at low levels of administered radioactivity. Combination treatment with the tumor-targeted interleukin 2 (L19-IL2, a clinical-stage immunocytokine) further expands the therapeutic window of 177Lu-OncoFAP-23 by potentiating its in vivo antitumor activity. Proteomics studies revealed a potent tumor-directed immune response on treatment with the combination. OncoFAP-23 and natLu-OncoFAP-23 exhibited a favorable toxicologic profile, without showing any side effects or signs of toxicity. Conclusion: OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of 177Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

Internal Nasal Valve Collapse Treatment by Endonasal Hyaluronic Acid Injection.

OBJECTIVE: Internal nasal valve collapse (IVC) is a common functional complication of rhinoplasty and injecting hyaluronic acid is one of the treatment options available, but its effectiveness has never been evaluated. The objective of this study was to assess the evolution of IVC after injection of hyaluronic acid using objective and subjective measures of nasal obstruction. STUDY DESIGN: A prospective interventional study was conducted. METHODS: Adult patients consulting for nasal obstruction after (septo)rhinoplasty and diagnosed with IVC were included. Patients underwent 4-phase rhinomanometry, completed nasal obstruction symptoms evaluation (NOSE) and visual analog scale (VAS) questionnaires and received hyaluronic acid injections. Measurements were repeated immediately, one month and one year later. The primary outcome measure was the proportion of patients below the rhinomanometric diagnostic threshold for IVC at one month. RESULTS: Among the 22 patients included, 20 (91%) had rhinomanometry measurements below the diagnostic threshold for IVC one month after injection. It decreased to 53% (8/15 patients) at one year post injection. The mean NOSE score decreased from 74.5 (± 18.0) before injection to 35.2 (± 23.3) after injection (p < 0.0001). The mean VAS score decreased from 7.0 (± 1.4) before injection to 3.4 (± 1.9) after injection (p < 0.0001). In these patients with post-(septo)rhinoplasty IVC, hyaluronic acid injection into the internal nasal valve substantially improved subjective and objective measures of nasal obstruction. CONCLUSION: These results suggest hyaluronic acid injection (performed as described) is an effective treatment for IVC and is an excellent alternative to surgical treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Next-Generation Therapeutic Antibodies for Cancer Treatment: Advancements, Applications, and Challenges.

The field of cancer treatment has evolved significantly over the last decade with the emergence of next-generation therapeutic antibodies. Conventional treatments like chemotherapy pose significant challenges, including adverse side effects. Monoclonal antibodies have paved the way for more targeted and effective interventions. The evolution from chimeric to humanized and fully human antibodies has led to a reduction in immunogenicity and enhanced tolerance in vivo. The advent of next-generation antibodies, including bispecific antibodies, nanobodies, antibody-drug conjugates, glyco-engineered antibodies, and antibody fragments, represents a leap forward in cancer therapy. These innovations offer increased potency, adaptability, and reduced drug resistance. Challenges such as target validation, immunogenicity, and high production costs exist. However, technological advancements in antibody engineering techniques provide optimism for addressing these issues. The future promises a paradigm shift, where ongoing research will propel these powerful antibodies to the forefront, revolutionizing the fight against cancer and creating new preventive and curative treatments. This review provides an overview of three next-generation antibody-based molecules, namely bispecific antibodies, antibody-drug conjugates, and nanobodies that have shown promising results in cancer treatment. It discusses the evolution of antibodies from conventional forms to next-generation molecules, along with their applications in cancer treatment, production methods, and associated challenges. The review aims to offer researchers insights into the evolving landscape of next-generation antibody-based cancer therapeutics and their potential to revolutionize treatment strategies.

Novel biopolymer spray formulation for drug delivery in precision dentistry.

Addressing the growing challenges of periodontal and peri-implant diseases, this study first reports a promising advancement in precision dentistry: an intricately formulated biopolymer spray designed for precise, localized drug delivery during tailored dental procedures. Poly (lactic-co-glycolic acid) (PLGA), recognized for its controlled release, biodegradability, and FDA-approved biocompatibility, forms the core of this formulation. Utilizing the double emulsion method, PLGA microparticles (PLGA-MPs) were loaded with dental antibiotics: sodium amoxicillin (AMX-Na), trihydrate amoxicillin (AMX-Tri), and metronidazole (Met). This antibiotic combination was thoughtfully selected to meet the distinctive requirements of the most impacting dental treatments. The newly developed biopolymer spray underwent thorough in-vitro analysis, revealing an optimized release curve for antibiotics over time, guaranteeing sustained therapeutic efficacy, and dose-dependent efficacy, accommodating personalized treatment approaches. The positive outcomes position the novel biopolymer spray formulation the leaders in advancing localized drug delivery during dental procedures. Moreover, the precise application and the tunable formulation meets the concept of precision medicine: in detail, this formulation represents a significant stride in dental therapeutics, significantly contributing to the predictability of dental implantology.

A comprehensive survey of the clinical trial Landscape on digital therapeutics.

Background: Digital therapeutics (DTx) is an emerging and groundbreaking medical intervention that utilizes health software to treat or alleviate various diseases, disorders, conditions, or injuries. Although the potential of digital therapy is enormous, it is still in its nascent stage and faces multiple challenges and obstacles. The purpose of this study is to provide an overview of all DTx-related clinical trials in ClinicalTrials.gov and to promote the advancement of DTx. Methods: Two reviewers and one expert evaluated data from all DTx clinical trials on ClinicalTrials.gov as of August 8, 2023. Trials utilizing digital therapeutics independently or in combination with traditional approaches were included. Incomplete trials and those lacking an evidence-based foundation were excluded. Basic information about product launches and primary outcome measures was extracted and analyzed. Results: A total of 280 eligible trials were categorized into treating a disease (141, 50.4 %), managing a disease (120, 42.9 %), and improving a health function (19, 6.8 %). The focus was primarily on mental and behavioral disorders, neurological disorders, and endocrine, nutritional, and metabolic disorders. The number of trials has been increasing annually, yet trial design and conduct remain inconsistent. Randomized controlled trials (RCTs) accounted for 67.5 % of completed trials, and 36 trials (12.9 %) involved products already approved for marketing. Conclusions: The growth in clinical studies on DTx underscores their potential in healthcare. However, challenges persist in standardization, regulation, and clinical efficacy. There is a need for a harmonized global classification of digital therapeutics and standardized clinical trial protocols to ensure efficacy and improve healthcare services.

Frequency and outcomes of treatment dose escalation with biologics in moderate-to-severe psoriasis: a Swedish register study.

BACKGROUND: The advent of biosimilars may increase the frequency of dose escalation with biologics in psoriasis. OBJECTIVE: To explore the frequency and outcomes of dose escalation with adalimumab etanercept, and ustekinumab. METHODS: Data were extracted from DermaReg-Pso, a psoriasis register in Stockholm, Sweden. The main exposure was treatment, and the main outcome was dose escalation. We describe outcomes with dose escalation by estimating drug survival and changes in the Psoriasis Area and Severity Index (PASI). RESULTS: 554 patients had 946 treatment episodes with adalimumab, etanercept, or ustekinumab. The cumulative incidence of dose escalation was 4.1 per 100 treatment years. The Hazard Ratios (HRs) for dose escalation with ustekinumab vs adalimumab and ustekinumab vs etanercept were 1.93 (95% CI: 1.25-2.98), and 2.20 (95% CI: 1.42-3.41), respectively. After dose escalation, the HRs for treatment discontinuation with adalimumab and etanercept compared with ustekinumab were 3.10 (95% CI: 1.56-6.18) and 7.15 (95% CI: 3.96-12.94), respectively. PASI was higher after compared to before dose escalation for etanercept (p = 0.036), but not for adalimumab (p = 0.832) or ustekinumab (p = 0.300). CONCLUSIONS: Dose escalation was comparatively more frequent with ustekinumab than with adalimumab or etanercept; however, treatment discontinuation after dose escalation was more common with adalimumab and etanercept than ustekinumab.

Competence Regulation in Streptococcus pneumoniae and the Competence-targeted Anti-pneumococcal Strategies.

Natural transformation refers to the process in which bacteria acquire new traits by uptaking naked DNA from the environment and integrating it into their genome through homologous recombination when they are in the specialized physiological state of competence. The natural transformation was first described in Streptococcus pneumoniae. Since Frederick Griffith first described natural transformations in S. pneumoniae in 1928, this phenomenon has been studied extensively. Induction of competence before natural transformation has been reported to involve about 10% of the pneumococcal genome. In addition to natural transformation, multiple physiological processes are involved, including biofilm formation, bacteriocin production, and fratricide. In this review, we summarized current knowledge about natural transformation in S. pneumoniae and described its competence regulation mechanism. This review also introduces the development of novel drugs and vaccines against S. pneumoniae infection by utilizing the existing knowledge of competence and natural transformation.

The Global Evolution and Impact of Systems Biology and Artificial Intelligence in Stem Cell Research and Therapeutics Development: A Scoping Review.

Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024. We identified an 8-10-fold increase in research output related to all three search terms between 2000 and 2021, with a 10-fold increase in AI-related production since 2010. Use of SysBio and AI still predominates in preclinical basic research with increasing use in clinically oriented translational medicine since 2010. SysBio- and AI-related research was found all over the globe, with SysBio output led by the United States (US, n=1487), United Kingdom (UK, n=1094), Germany (n=355), The Netherlands (n=339), Russia (n=215), and France (n=149), while for AI-related research the US (n=853) and UK (n=258) take a strong lead, followed by Switzerland (n=69), The Netherlands (n=37), and Germany (n=19). The US and UK are most active in SCs publications related to AI/ML and AI/DL. The prominent use of SysBio in ESC research was recently overtaken by prominent use of AI in iPSC and MSC research. This study reveals the global evolution and growing intersection between AI, SysBio, and SC research over the past two decades, with substantial growth in all three fields and exponential increases in AI-related research in the past decade.