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Despite substantial advancements in antiretroviral therapy (ART), HIV-related mortality remains a pressing challenge, particularly in resource-limited settings. In countries like Ethiopia, there is a critical gap in tools to predict mortality risk among patients receiving ART, which limits timely clinical decision-making and intervention. Addressing this gap, the present study aimed to develop a validated mortality risk prediction model for adult HIV patients receiving ART at Felege Hiwot Comprehensive Specialized Hospital (FHCSH). A retrospective cohort study was conducted among 777 HIV-positive adults receiving ART at FHCSH. Participants were selected using the "rule of thumb" for predictive modeling. Secondary clinical data were extracted, cleaned, and analyzed using Epi Info and R software. Logistic regression was employed to identify the significant prognostic determinants of mortality. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. A nomogram was developed to visualize the risk estimates. Internal validation was performed using bootstrapping method, and decision curve analysis (DCA) was conducted to assess clinical utility. The overall incidence of mortality among ART patients was 12.6% (95% CI 10.2-15.1%). Six key prognostic factors-WHO clinical stage, functional status, baseline ART regimen, duration of treatment, adherence level, and presence of comorbidities-were incorporated into the final prediction model. The nomogram model demonstrated excellent discriminative ability, with an AUC of 0.968 (95% CI 0.951-0.983) for the original model and 0.967 (95% CI 0.947-0.987) for the reduced model. At the optimal cut-off point (0.1667), the model achieved 93.3% accuracy, 87.8% sensitivity, and 94.1% specificity. DCA indicated strong net clinical benefit across a wide range of threshold probabilities (0.1-0.8). This study developed a robust and well-performing mortality risk prediction model for HIV patients on ART, incorporating six easily obtainable clinical indicators. The model, presented as a nomogram, showed excellent discrimination and calibration, providing a practical tool for frontline clinicians to stratify mortality risk and tailor interventions. However, external validation through large-scale, multicenter prospective studies is recommended before routine clinical application.

Childhood underweight and low body mass index are major public health concerns. There is no definitive evidence on the dosage adjustment of Cyproheptadine as an appetite stimulant. This study aimed to evaluate the effect of Cyproheptadine on Body Mass Index (BMI) in underweight children and assess its associated adverse effects. This randomized double-blinded clinical trial study was conducted on thin children aged 2 to 10 years. The study was conducted on three groups of 92 children receiving low-dose Cyproheptadine, standard-dose Cyproheptadine, or placebo. Children were assessed monthly for 4 months for changes in anthropometric indices and treatment-related side effects. Data were analyzed using SPSS version 23 Results: Mean BMI showed significant between-group differences at three and four months (p = 0.001 and p < 0.001, respectively). Drowsiness occurred significantly more often in the standard- dose group than in the low-dose group at all visits (p < 0.001). No significant differences between groups in terms of irritability (p > 0.05). Mood swings were consistently more frequent in both Cyproheptadine groups than in the placebo group (p = 0.03). These results are consistent with prior evidence supporting Cyproheptadine's role in promoting weight gain and add important insight into dose-related safety. However, the short follow-up period limits conclusions about long-term outcomes. Low-dose cyproheptadine is an effective and safer therapeutic option for increasing BMI in children, offering efficacy comparable to the standard dose with fewer adverse effects. These results also highlight the necessity of long-term monitoring to ensure sustained efficacy and safety.

The goal of achieving clinical operational tolerance in liver transplantation has sparked significant interest, driven by the desire to mitigate the long-term adverse effects of immunosuppression. Advances in understanding the immunological mechanisms underpinning operational tolerance in liver transplantation have highlighted the central role of regulatory T cells and tolerogenic dendritic cells. These cells actively suppress effector immune responses and aid in achieving operational tolerance. Immunosuppressive medication differentially influences the expansion, survival, and function of these cells, demonstrating the importance of understanding the potential of immunosuppressive regimens to optimize the possibility of achieving an immunosuppression-free state. The potential of stepwise immunosuppressive reduction to achieve operational tolerance without compromising graft function has been demonstrated. The immunosuppressive withdrawal protocols underline the feasibility and safety of immunosuppressive withdrawal in selected liver transplant recipients, highlighting factors such as time since transplantation, recipient age, and gender as strong predictors of success. Furthermore, minimization of immunosuppressive, even early post transplantation, has been shown to be successful and sets the stage for successful immunosuppression withdrawal later. This review highlights the necessity to optimize immunosuppressive regimens by demonstrating its possibility to aid in achieving minimal immunosuppressive to maximize success rates of drug withdrawal and diminish the cumulative immunosuppressive related complications to increase the quality of life of liver transplant recipients.

Pathogenic variants in the COL4A4 gene lead to Alport syndrome, a hereditary kidney disorder characterized by deficiencies in the glomerular basement membrane (GBM), progressive renal failure, and associated visual and auditory dysfunctions. This study is aimed at detecting genetic variants and conducting an integrative network analysis to elucidate their involvement in Alport syndrome and chronic kidney disease (CKD). The enrolled patients were biological sisters. Clinical and pathological data were collected using laboratory tests. Genetic testing was performed to identify the variants via whole-exome sequencing (WES). The pathogenicity of the detected variant was confirmed using different computational approaches. The detected variants were classified according to the ACMG criteria. The interaction networks of CKD, Alport syndrome, and COL4A4 were examined using STRING v11.5, whereas pathways were analyzed by KEGG and STRING pathways analysis. Patients were diagnosed with CKD of Stage 5. The ultrasound results were not clear due to kidney fibrosis. WES revealed an 18-base pair deletion in the COL4A4 gene (chr2: g.227958874_227958891del). The detected variant was classified as pathogenic by ACMG criteria. Online Mendelian Inheritance in Man (OMIM) reveals that the variant in COL4A4 is due to autosomal recessive Alport syndrome 2. Sensorineural hearing loss was observed in two family members of the patients. These results show the existence of Alport syndrome in their family. The disease-protein interaction by STRING reveals that the COL4A4 protein is strongly associated with both CKD and Alport syndrome diseases. KEGG analysis indicates a consistent association of PI3K-Akt and AGE-RAGE pathways among both diseases. Dysfunction of COL4A4 leads to disruptions in GBM structure and signaling, which hasten CKD in Alport syndrome. Genetic testing is essential for identifying the exact cause of the disease, which aids in early diagnosis and control to spread within families.

The vesicular acetylcholine transporter (VAChT), primarily located in presynaptic cholinergic nerve terminals, serves as a key target in neuroimaging studies and neuropathological assessments to quantify cholinergic neuron decline. [18F]VAT has been demonstrated to serve as a selective and specific radiotracer to quantify VAChT expression in the brains of patients with neurological diseases. Herein, we report the absolute configuration of the chemical structure and development of a straightforward cGMP protocol to produce [18F]VAT for clinical use. The absolute configuration was unambiguously determined by X-ray crystallography of the VAT phenolic analogue, establishing its (2R,3R) stereochemistry for the first time. The radiotracer production was successfully accomplished using a simple one-pot and one-step approach under cGMP conditions, achieving an average radiochemical yield of 16.9% &#xb1; 1.8% (decay-corrected to the end of synthesis), a molar activity of 61.9 &#xb1; 19.6% GBq /&#x3bc;mol, with a total synthesis time of approximately 60 minutes (n = 3). The final product met all established quality control criteria for human use.

Background Knee joint disorders are a major cause of musculoskeletal morbidity and functional disability worldwide, involving a broad spectrum of traumatic, degenerative, cystic, and neoplastic pathologies. Accurate evaluation of these conditions is essential for appropriate clinical assessment. MRI provides detailed visualization of intra-articular and periarticular structures due to its superior soft tissue contrast and multiplanar capability. However, there remains a need for region-specific observational data describing the spectrum of MRI findings in routine clinical practice. Materials and methods This retrospective observational study was conducted in the Department of Radiodiagnosis at Hi-Tech Medical College and Hospital, Rourkela, India, following institutional ethics approval. A total of 236 patients who underwent MRI of the knee between August 2024 and July 2025 were included. Patients referred with clinical suspicion of knee joint pathology were evaluated. MRI findings were analyzed to determine the distribution of knee joint pathologies and their association with demographic variables. Results Of the 236 patients, 149 (63.13%) were males, and 87 (36.87%) were females. Ligamentous and meniscal injuries were the most common findings, observed in 134 patients (56.78%), with a predominance among younger male patients. Anterior cruciate ligament tears were the most frequent ligamentous injury, followed by medial meniscus tears. Osteoarthritis was identified in 47 cases (19.92%) and was more frequently observed in older female patients. Baker's cysts were observed in 25 cases (10.59%), fractures in 20 cases (8.47%), and malignant neoplasms in 10 cases (4.24%). Among fractures, patellar fractures were the most common pattern. Among malignant lesions, synovial sarcoma was the most frequently identified tumor. Conclusions Knee joint pathologies demonstrated a distinct distribution pattern, with ligamentous and meniscal injuries predominating in younger males and degenerative changes more frequent in older females. Within the framework of this observational study, MRI facilitated detailed characterization of a wide spectrum of knee abnormalities; however, in the absence of comparative or outcome-based data, conclusions regarding diagnostic accuracy or clinical impact cannot be established. These findings provide context-specific insights into the epidemiological and imaging profile of knee joint pathologies and may serve as a foundation for future prospective and comparative studies.

Staphylococcus aureus (S. aureus) is a commensal microorganism that is part of the normal human flora but has the potential to cause a wide range of infections, from superficial skin conditions to life-threatening systemic diseases such as bacteremia. The aim of this study was to evaluate the epidemiological characteristics and antimicrobial resistance patterns of S. aureus strains isolated between 2019 and 2024 at a tertiary hospital in Mogadishu, Somalia. In this retrospective study, a total of 1,381 S. aureus isolates obtained from various clinical specimens submitted from different departments to the Medical Microbiology Laboratory were analyzed. The isolates were identified using standard microbiological methods, and antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method in accordance with Clinical and Laboratory Standards Institute (CLSI) criteria. Data were statistically analyzed, and a p-value of <&#x2009;0.05 was considered statistically significant. Of the 1,381 S. aureus isolates, 670 (48.51%) were identified as methicillin-resistant Staphylococcus aureus (MRSA), while 711 (51.49%) were methicillin-susceptible Staphylococcus aureus (MSSA). Of the isolates, 55.03% were obtained from male patients and 44.97% from female patients. The highest isolation rate was observed in the 18-64 year age group. Among clinical specimens, wound samples (47.57%) and blood cultures (37.14%) were the most common. Both MRSA and MSSA isolates were most frequently recovered from outpatient clinics, and a statistically significant difference was observed in distribution across clinical departments (p&#x2009;=&#x2009;0.004). Antimicrobial susceptibility analysis revealed high resistance rates among MRSA isolates to penicillin G (98.61%), erythromycin (71.11%), and tetracycline (66%), while MSSA isolates showed high resistance to penicillin G (91.51%), tetracycline (53.57%), and levofloxacin (49.61%), while MSSA isolates showed high resistance to penicillin G (91.51%) and tetracycline (53.57%). Very low resistance rates were observed for linezolid, vancomycin, and quinupristin-dalfopristin. S. aureus remains a significant pathogen in the region, particularly due to the high prevalence of MRSA strains. The elevated resistance rates identified in this study underscore the need to tailor empirical treatment strategies based on local antibiogram data. Continuous surveillance and effective antimicrobial stewardship programs are critical for controlling the emergence and spread of antimicrobial resistance.

Diabetic foot ulcers (DFUs) are a severe complication of diabetes, with current standard care often failing to prevent chronic morbidity and amputation. This narrative review examines the therapeutic potential of adipose-derived stem cells (ADSCs) for DFUs treatment. ADSCs promote healing through paracrine secretion of growth factors, immunomodulation, and stimulation of angiogenesis, as demonstrated in promising preclinical and early clinical studies. We outline these mechanisms, discuss the emerging role of ADSC-derived exosomes as a potentially safer alternative, and summarize key clinical findings. However, significant challenges remain, including potential risks of tumorigenicity, donor cell variability, and a lack of standardized protocols. While ADSC therapy represents a highly promising regenerative approach for DFUs, its safety and efficacy must be firmly established through more rigorous preclinical studies and large -scale randomized controlled trails before broad clinical adoption. This review concludes that while ADSC therapy is a highly promising regenerative approach for DFUs, its translation to clinical practice necessitates further rigorous investigations to overcome existing translational barriers.

Anthracyclines are potent therapeutic agents widely used in cancer treatment and other medical applications, including infectious diseases and inflammatory disorders. However, their clinical utility is often restricted by severe systemic toxicity, poor biodistribution, and the emergence of multidrug resistance (MDR). To address these limitations, nanocarrier-based drug delivery systems have been developed to improve therapeutic selectivity and safety. Among them, liposomal formulations have achieved the highest level of clinical translation. FDA-approved liposomal anthracyclines such as Doxil&#xae; (doxorubicin), DaunoXome&#xae; (daunorubicin), and Vyxeos&#xae; (daunorubicin-cytarabine) have demonstrated enhanced pharmacokinetics, reduced cardiotoxicity, and improved therapeutic outcomes compared with conventional formulations. Beyond liposomes, alternative and emerging nanocarriers, including polymeric nanoparticles, micellar systems, dendrimeric carriers, and hybrid lipid-polymer constructs, are being explored to achieve higher drug loading, controlled release, and targeted tissue penetration. These formulations also show promise for antimicrobial and immunomodulatory therapies. Nevertheless, key challenges such as safety concerns, large-scale production, and regulatory barriers continue to impede broad clinical adoption. This review provides a comprehensive overview of liposomal and alternative nanoformulations for anthracyclines, discussing their advantages, limitations, and clinical potential while addressing the key challenges that must be overcome for their successful translation into widespread medical use, while also highlighting emerging biohybrid, extracellular vesicle-based, and stimuli-responsive systems that represent leapfrogging innovations in anthracycline delivery.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune disorder increasingly recognized in children. We aimed to evaluate cerebrospinal fluid (CSF) anti-NMDAR antibody levels in pediatric encephalitis, and to assess their diagnostic and prognostic utility in relation to clinical, laboratory, and neuroimaging features METHODS: In this prospective observational study, 85 children with encephalitis admitted to the pediatric intensive care unit were evaluated. Patients were categorized into Group I (n&#x2009;=&#x2009;37) with anti-NMDAR encephalitis and Group II (n&#x2009;=&#x2009;48) with non-anti-NMDAR encephalitis. Clinical manifestations, CSF findings, Electroencephalogram (EEG), and CSF anti-NMDAR antibody levels (measured by ELISA) were analyzed. Receiver operating characteristic (ROC) curves assessed diagnostic performance RESULTS: Group I demonstrated significantly higher rates of psychiatric symptoms, seizures, abnormal movements, and speech disturbances than Group II. EEG abnormalities, particularly extreme delta brush, were more common in anti-NMDAR encephalitis. CSF anti-GluN1 antibody levels correlated positively with alanine aminotransferase(ALT), platelet count, and Glasgow Coma Scale score (GCS), and negatively with CSF neutrophils and protein. Antibody levels were significantly elevated in Group I, with ROC analysis showing high sensitivity and specificity for diagnosis CONCLUSION: CSF anti-NMDAR antibody measurement is a robust diagnostic biomarker in pediatric encephalitis. Early detection may facilitate timely immunotherapy and improve outcomes. This study demonstrates that CSF anti-NMDAR antibody testing improves both the diagnosis and prognosis of pediatric encephalitis. Antibody positivity was associated with distinct clinical and neuroimaging features, supporting earlier recognition and initiation of immunotherapy. Incorporating antibody testing into pediatric practice may enhance patient outcomes and advance the management of autoimmune encephalitis in children.

Foods fortified with probiotics are a fast-emerging field at the crossroads of food technology, nutritional biochemistry and microbiome science. The increased interest in the gut microbiota as a key controller of host metabolism, immunity and overall homeostasis has led to the creation of diets that provide key nutrients with live and beneficial microbes. Compared to the conventional dietary supplementation, there are improved microbe stability, bioavailability, and microbe-nutrient interactions of probiotic fortification of food matrices. This review is a summary of the literature on the impact of probiotics on the host immunological and metabolic signalling pathways, intestinal barrier functioning, and gut microbiota composition. The biological mechanisms of interaction of probiotics with the intestinal microenvironment are specifically focused on the production of short-chain fatty acids, expulsion of pathogens, the regulation of immune cells, and the communication of the gut-brain axis. New information that can be used to correlate the administration of probiotics with the improvement of gastrointestinal health, systemic inflammation, metabolic maintenance and neurobehavioral phenotypes is narratively synthesized based on available preclinical and clinical evidence. The opportunities of probiotic-enriched functional foods have been highlighted in this review as a strategic tool of disease prevention and health promotion in the context of the mechanistic knowledge in combination with translational health outcomes. The complexity in the interactions between microbial delivery systems and host physiology is the clue to the best efficacy, safety and the future innovation in the development of functional foods.

&#x2009;: Cystic fibrosis (CF) is likely underdiagnosed in Caribbean populations due to non-representative cystic fibrosis transmembrane conductance regulator (CFTR) variant screening panels, limited newborn screening programs, and structural healthcare barriers. Data from 2022 indicate substantial populations with European ancestry in Puerto Rico (1.4&#x2009;M, 42.7%) and the Dominican Republic (1.4&#x2009;M, 57.9%), yet the true burden of CF in the broader Caribbean remains largely undocumented. Current diagnostic frameworks, largely based on European-derived CFTR variant distributions, fail to capture the true burden of CF in Caribbean populations, leading to underestimated prevalence and delayed or missed diagnoses. To synthesize registry, clinical, and published data to identify barriers to accurately assessing CF prevalence in Caribbean populations. This narrative literature review integrates CF registries, published data on CFTR variant distribution, population ancestry data, and clinical observations from CF centers in Puerto Rico and the Dominican Republic. Clinical insights were derived from pediatric patients evaluated at the Pediatric Rare Lung and Asthma Institute in Puerto Rico and the CF Clinic at Robert Reid Cabral Children's Hospital in the Dominican Republic. CFTR variant patterns differ from those in the United States, with higher frequencies of rare variants such as p.Ala559Thr. Standard screening panels may miss these variants, contributing to underdiagnosis. Limited newborn screening, misdiagnosis, and restricted access to CFTR modulator therapies further exacerbate disparities. Structural, diagnostic, and genetic factors hinder accurate CF prevalence estimates in the Caribbean, highlighting the need for region-specific research, improved screening, and expanded access to therapies.

Haskap berries have great potential as a superfood due to high polyphenolic content which confers both anti-inflammatory and antioxidant activity. These health impacts are mitigated, at least in part, by the gut microbiome as most ingested polyphenols pass to the large intestine for microbial enzymatic action and conversion to secondary phenolic metabolites. These microbial actions mediate both the bioavailability and the bioefficacy of Haskap-derived phenolics. However, clinical intervention trials characterizing the impact of long-term Haskap consumption on human health and the interaction between Haskap-derived phenolics and the gut microbiome are limited. This study aims to determine the impact of Haskap consumption on gut microbiome composition, gut microbial and serum metabolites, and other health outcome metrics in a cohort of adults with both low and high risk of metabolic syndrome. This is a four-armed, randomized, triple-blind, placebo-controlled clinical trial conducted in a cohort of adults with both low and high risk of metabolic syndrome. A total of 120 participants (60 metabolically healthy, 60 metabolically unhealthy) will be randomized in a 1:1 ratio to consume a daily dose of either Haskap or placebo juice for 8 weeks. Outcome measures will be collected before and after the intervention period to determine the health impacts of Haskap in both groups. Primary outcome measures include fasting blood markers of glucose and lipid metabolism and inflammation, fat oxidation rates during submaximal exercise, 16S rRNA fecal microbial composition data, and mass spectrometry-acquired fecal and serum metabolomic data. Secondary outcome measures include anthropometric and sleep quality measures as well as acute and habitual dietary intake data. Investigating how the gut microbiome influences the health benefits of consuming Haskap berries will help elucidate potential mechanisms of Haskap-induced metabolic health benefits and help inform the development of effective strategies to decrease metabolic disease risk through Haskap consumption. ClinicalTrials.gov NCT06546020. Registered on 1 August 2024.

Endoplasmic reticulum stress (ERS), caused by excessive buildup of misfolded proteins in the ER lumen, has emerged as a major contributor to diabetes mellitus (type-1 and type-2; T1DM and T2DM), leading to &#x3b2;-cell dysfunction, insulin resistance, and related comorbidities. In this review, we aim to characterize the signal transduction pathways in normal versus diseased conditions and their impact on the development of insulin-dependent and insulin-independent diabetes. Evidence on ERS and diabetes were searched in MEDLINE and Google scholar databases using search strings that incorporated synonyms of ERS, diabetes, &#x3b2;-cell dysfunction and insulin resistance and their impact in disease progression. Our search was guided by the pertinent keywords as mentioned in the "keywords" section, that encompassed past twenty-five years of body of literature in this field as evident from Urano et al. 2000 till Sue et al. 2025. Our results and conclusion are the distillation of past two and half decades of scientific research dedicated towards understanding the biology of ERS dependent diabetes. The ERS-induced Unfolded Protein Response (UPR), comprising of three signaling cascades, is pivotal in either protecting against or contributing to the pathophysiology of T1DM and T2DM. Clinically, ERS manifests as insulin resistance, heightened inflammation, and &#x3b2;-cell destruction. Consequently, ERS effectors and proteins involved in the UPR pathways have become attractive targets for pharmacological investigation. We also review some of the protein biomarkers of ERS dependent diabetes and relevant in vivo/ex vivo models used in clinical versus preclinical settings, as well as the latest state-of-the-art targeted molecular and cellular therapies that are currently being tried for the diabetic patients.

Ischemic stroke in Saudi Arabia arises in a highly consanguineous population with a distinctive genetic architecture, likely enriching rare coding variants that influence stroke risk. Yet the contribution of these variants to stroke susceptibility, age at onset, and subtype patterns in this setting remains incompletely defined. We analyzed whole-exome sequencing data from 514 stroke patients in a case only study design. Gene-based rare variant burden analyses was performed using SAIGE-GENE+ burden and SKAT-O tests across predefined phenotype contrasts within the cohort, stroke severity (modified Rankin Scale, mild&#x2009;<&#x2009;3 vs. severe&#x2009;&#x2265;&#x2009;3 ,), age at onset (early-onset&#x2009;<&#x2009;25 years vs. late-onset&#x2009;>&#x2009;45 years; mid-life onset&#x2009;<&#x2009;45 vs.&#x2009;>&#x2009;45), etiological subtypes (TOAST classification), and vascular imaging patterns (intracranial vs. extracranial).Post-association functional annotations included GTEx expression, gnomAD constraint metrics, and draggability insights. Gene-level associations at a suggestive threshold (p&#x2009;<&#x2009;0.005) identified several candidates including HSP90AB1, PRR23A, and LRRC42 (severity and age-at-onset); POGZ and SMIM34 (age-at-onset); and COL9A3, DCP1B, and ADGRV1 (imaging and etiology subtypes). The highlighted genes showed varying expression across brain and vascular tissues and intolerance to loss-of-function variation. Notably, HSP90AB1, a molecular chaperone highly expressed in the brain and vasculature, has small-molecule inhibitors, supporting its potential relevance to stroke biology. Our findings identify exploratory candidate gene-level signals across clinically defined ischemic stroke phenotypes based on case-only within-cohort comparisons, in underrepresented population. These results should be considered hypothesis-generating and require replication and functional validation before biological or clinical inferences can be made.

Antiphospholipid syndrome (APS) is an autoimmune disease defined by thrombotic or obstetrical clinical manifestations and the persistent presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein 1 antibodies. Obstetric APS (OAPS) is associated with pregnancy morbidity, including early recurrent pregnancy loss (RPL), preeclampsia, premature birth and stillbirth. Treatment regimens for women with OAPS are designed to optimise pregnancy outcomes. It is still debated which intervention results in the most optimal pregnancy outcome. This scoping review examines treatment options for women with OAPS presenting with RPL based solely on randomized controlled trials (RCTs) reporting pregnancy outcomes. A systematic search identified 1,234 studies published up to January 2026, from which 14 RCTs met the inclusion criteria: pregnant women with APS defined as persistent aPL positivity and RPL (&#x2265;2) receiving therapeutic intervention with live birth as the primary outcome. These RCTs, published between 1992 and 2017, included 1,878 participants. Secondary outcomes, including birth weight, preeclampsia, preterm delivery, and bleeding were also analyzed. Different treatment options such as low-dose aspirin (LDA), unfractionated heparin, low molecular weight heparin (LMWH), corticosteroids and intravenous immunoglobulin were used in the clinical trials. Antithrombotic therapy (LDA+LMWH) was associated with higher live birth rates compared with the other evaluated strategies. However, this finding is based on a small number of heterogeneous RCTs and is disproportionately driven by a single large trial. Consequently, substantial uncertainty remains. High-quality, adequately powered RCTs are urgently needed to provide robust evidence for optimal OAPS management.

Injectable dermal fillers represent a rapidly evolving class of soft-tissue biomaterials whose clinical behavior is determined by their underlying material properties. Despite widespread use in aesthetic medicine, the relationships between structure and behavior that dictate filler performance remain incompletely synthesized across material classes. This review examines the material science foundations of modern dermal fillers, spanning hyaluronic acid formulations, collagen-based materials, and biostimulatory systems, including calcium hydroxylapatite, poly-L-lactic acid, and polycaprolactone. Emphasis is placed on the material parameters that govern filler behavior in vivo, such as polymer chemistry, crosslinking methodology, particulate microstructure, and degradation kinetics. These factors collectively determine key rheological characteristics such as storage modulus (G'), loss modulus (G&#x2033;), cohesivity, and injectability. In turn, these influence material stability, tissue integration, and resistance to mechanical deformation within dynamic facial environments. Recent advances in formulation strategies, including multiphasic fillers, microspheres, and hybrid systems, illustrate how modification of microstructure can be leveraged to improve durability, biocompatibility, and tissue remodeling potential. This review establishes a mechanistic framework linking filler composition to rheological performance and degradation behavior. As the first part of a 2-part review, the focus here is on the material science and bioengineering principles that inform filler behavior in order&#xfeff; to provide the scientific foundation for the clinical decision-making framework explored in Part B.

The development of mRNA vaccines has significantly advanced global health during the COVID-19 pandemic. However, translating effective vaccine doses from preclinical animal models to human clinical use remains poorly understood. In this study, we evaluated antibody responses and repertoire diversity across different BNT162b2 mRNA vaccine doses in mice, while comparing the results with human data through mathematical modeling. We observed that 1&#xa0;&#x3bc;g BNT162b2 dose regimen induced a persistent antibody response and broad antibody repertoire for up to 16&#xa0;weeks in mice. Conversely, 0.05&#xa0;&#x3bc;g BNT162b2 dose regimen resulted in waning antibody responses and narrowed antibody repertoires over the same period, resembling responses observed in humans vaccinated with 30&#xa0;&#x3bc;g BNT162b2 dose regimen. An empirical dose translation approach revealed a discrepancy in dose relevance between the 1&#xa0;&#x3bc;g commonly used in the in vivo mice model and the 30&#xa0;&#x3bc;g used for vaccination in human. Therefore, it is crucial to re-evaluate the appropriate mRNA vaccine dose for in vivo mice models to accurately reflect human responses.

Alzheimer disease (AD) is the most common cause of dementia in the world with the prevalence expected to increase threefold to 152.8 million people by 2050. The current medications provide a short-term ameliorative effect, and this requires development of disease-modifying treatments, which address the biological pathogenesis. This review assesses the changing neuropharmacological environment offering a critical analysis of anti-amyloid monoclonal antibodies and investigates the so-called expanding frontier of non-amyloid targets. It also examines the approaches of clinical trials and the trend of biomarker-based patient selection and precision medicine. Although &#x3b2;-site APP-cleaving enzyme 1 (BACE1) and secretase inhibitors did not achieve success in clinical trials because of mechanism-based toxicity and cognitive impairment, new monoclonal antibodies such as lecanemab and donanemab have shown high amyloid plaque clearance and reduced cognitive deterioration. Nevertheless, the treatments are associated with amyloid-related imaging abnormalities (ARIA). In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF). AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails. The future lies in precision neuropharmacology, where genetic stratification and individual biomarker analysis are used to provide the correct treatment at the most appropriate biological stage.