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This study investigated the haemodynamic effects by simulating simplified cerebrovascular at different stenosis levels. To improve the understanding of haemodynamic changes due to atherosclerosis, computational fluid dynamics (CFD) simulations are employed to visualise wall shear stress (WSS), pressure distribution, and flow rate within arterial models. Three different degrees of arterial atherosclerosis, specifically 25%, 50% and 75% plaque thickness have been examined. Findings show that in the severe atherosclerosis of 75%, blood flow velocity through the plaque undergoes a significant change, leading to low pressure due to extreme narrowing and resulting turbulent flow. Moreover, WSS contours reveal extensive and severe red zones when atherosclerosis reaches 75%, especially within and beyond the severely constricted region. Although the individual parameters were visualised, the velocity-pressure correlation for each atherosclerosis level showed velocity peaks around 10 m/s for 50% plaque and sharply increasing to nearly 100 m/s for 75% plaque. In mild atherosclerosis (25% plaque), both velocity and pressure profiles remain relatively stable. This study offers deeper insights and understanding on how atherosclerosis alters cerebral circulation, potentially enhancing diagnostic accuracy and treatment strategies for stroke prevention.

In the injection molding industry, the shift toward small-batch production has led to a greater variety of products and smaller batch sizes, necessitating frequent mold changes and efficient quality control, which still largely relies on human operators. This study proposes a comprehensive methodology for evaluating and comparing deep learning-based automatic optical inspection (AOI) strategies to detect complex surface defects in injection-molded parts. Three inspection setups were assessed: static frontal imaging, belt conveyor inspection, and robotic-assisted inspection. The findings reveal clear differences in defect detection capabilities among the methods, with the robotic-assisted approach demonstrating superior performance, achieving higher defect detection accuracy due to its flexibility in optimizing camera angles and positions. The proposed methodology serves as a workflow to systematically evaluate and optimize inspection setups across different parameters, enabling informed decisions about AOI systems design. This research contributes to narrowing the gap between the development of advanced detection algorithms and their industrial application, offering insights into the strategic implementation of AI technologies in quality control processes and enhancing the automatic detection of challenging defects.

Cerebral vasospasm is a rare but devastating complication following intracranial tumor surgery, particularly in pediatric suprasellar lesions such as craniopharyngiomas. Delayed cerebral ischemia secondary to postoperative vasospasm remains insufficiently recognized and may result in fatal neurological injury. We report the case of a 5-year-old girl who underwent gross total resection of a cystic suprasellar craniopharyngioma through a subfrontal approach without intraoperative vascular injury. The immediate postoperative course was uneventful. On postoperative day 6, the patient developed sudden refractory status epilepticus associated with rapid neurological deterioration and bilateral fixed mydriasis. Brain computed tomography (CT) revealed extensive left hemispheric ischemia with severe cerebral edema. CT angiography demonstrated marked narrowing of the A1 + M1 segment of the left middle cerebral artery, consistent with malignant cerebral vasospasm. Despite intensive care management, the patient progressed to brain death and subsequently died. Delayed malignant cerebral vasospasm following pediatric craniopharyngioma resection is an unpredictable and potentially fatal complication that may occur even in the absence of intraoperative vascular injury. Prompt recognition of delayed neurological deterioration and early vascular imaging are crucial to improve diagnostic and therapeutic management.

Peripheral artery disease (PAD) is a prevalent and disabling vascular condition characterized by progressive atherosclerotic narrowing and stiffening of peripheral arteries. Arterial stiffness, most accurately measured by pulse wave velocity (PWV), has gained prominence as a critical biomarker in the assessment and management of PAD. Unlike traditional diagnostic tools that focus primarily on anatomical lesions, PWV offers dynamic insights into vascular function, elasticity, and systemic cardiovascular risk. Elevated PWV has been consistently associated with adverse outcomes in PAD patients, including critical limb ischemia, restenosis following angioplasty, amputation, and cardiovascular mortality. It not only reflects disease severity but also facilitates early risk stratification, informs treatment selection, and enables monitoring of therapeutic efficacy. Studies have shown that reductions in arterial stiffness following angioplasty, pharmacological therapy, or lifestyle interventions correlate with improved limb perfusion and long-term clinical outcomes. Moreover, in elderly PAD patients, arterial stiffness often coexists with frailty-another key predictor of poor prognosis. Emerging evidence suggests that both conditions may share pathophysiological pathways related to vascular aging and sarcopenia. The integration of PWV into routine PAD evaluation may thus offer a more holistic understanding of patient risk and resilience. Given its diagnostic, prognostic, and therapeutic utility, arterial stiffness-particularly as assessed by PWV-should be considered an essential parameter in PAD management. Incorporating this measurement into clinical practice holds significant potential to improve individualized care, reduce complications, and enhance overall patient outcomes.

A three-year-old neutered female Bernese mountain dog was referred for evaluation of multiple congenital cardiac abnormalities. Transthoracic echocardiography demonstrated features consistent with type A pulmonic stenosis, including a normal pulmonary valve annulus, an increased transvalvular pressure gradient, systolic doming of thickened and fused pulmonary valve leaflets, and concentric right ventricular hypertrophy. Additionally, a focal aneurysmal dilation arising from the intermediate pulmonary valve leaflet was identified. Furthermore, a concurrent left-to-right shunting patent ductus arteriosus was detected. Computed tomography confirmed thickening of the pulmonic valve, narrowing of the sinotubular junction, and thin-walled, contrast-enhancing saccular dilation originating of the intermediate pulmonary valve sinus. These findings supported the diagnosis of a pulmonary valve sinus aneurysm associated with severe type A pulmonic stenosis and patent ductus arteriosus.

Polyarteritis nodosa (PAN) is a rare vasculitis affecting predominately medium-sized vessels. Our evolving understanding of PAN, including the role of HBV and discovery of monogenic variants such as deficiency of adenosine deaminase 2 (DADA2), has resulted in idiopathic PAN becoming a very rare condition with an annual incidence of 0.6-19.9/million. The investigative approach is to assess organ involvement and confirm the diagnosis either by imaging or biopsy. Conventional catheter angiography is being replaced by CT or MR angiography, which provide increasingly good resolution of the typical fusiform narrowing and aneurysm. ANCA-associated vasculitis (AAV) should be excluded. DADA2 is being more frequently identified as causing a PAN-like illness, especially in children; cases presenting in adulthood are now recognised. In children and most adults, genotyping for DADA2 should be undertaken. There are no high-quality randomised controlled trials of treatment in idiopathic PAN. Current approaches have been adapted from those used to treat other types of vasculitis. The five-factor score may be used to stratify patients to identify those needing intensive therapy with glucocorticoids combined with CYC. In order to reduce the burden of glucocorticoid toxicity, the ACR has advocated the use of immunosuppressive drugs in addition to steroids in those not initially receiving CYC. Unlike AAV, there appears to be little role for rituximab in the treatment of idiopathic PAN, although it is occasionally used as salvage therapy. HBV-associated PAN is treated with immunosuppression and antiviral therapy. There is reasonably good evidence to support the use of anti-TNF to treat DADA2.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache and reversible segmental cerebral arterial constriction. Although neurological complications are well recognized, concurrent extracerebral vasoconstriction remains under appreciated. A 53-year-old woman presented with sudden chest tightness immediately followed by a thunderclap headache. Initial brain computed tomography and magnetic resonance imaging showed no hemorrhage or infarction; however, magnetic resonance angiography demonstrated multifocal cerebral arterial narrowing, consistent with RCVS. During hospitalization, she developed recurrent nonaneurysmal subarachnoid hemorrhages (SAHs) on days 2 and 4. No bleeding source was identified on serial angiography. Recurrent episodes of chest tightness prompted coronary angiography with acetylcholine provocation, which revealed severe coronary vasospasm, establishing the diagnosis of vasospastic angina (VSA). Treatment with benidipine and nicorandil was initiated thereafter, and no recurrence of either cardiac or neurological symptoms was observed, with complete resolution of cerebral vasoconstriction on follow-up imaging. This case highlights a rare but clinically important association between RCVS, recurrent nonaneurysmal SAH, and coronary VSA confirmed by pharmacologic provocation. Although each condition is potentially reversible, their coexistence supports the concept of systemic vasoconstriction syndrome and underscores the need for vigilance regarding extracranial vascular involvement in patients with RCVS. Early recognition and targeted vasodilator therapy may be essential to prevent serious neurological and cardiovascular complications.

Comparative data on vessel preparation using intravascular Shockwave lithotripsy (Johnson and Johnson, New Brunswick, NJ) or the 355-nm Auryon laser (Angiodynamics, Latham, NY) in calcified femoropopliteal arterial disease is limited. This is a retrospective, single-center study evaluating the 30-day safety and effectiveness of the 355-nm laser system versus Shockwave lithotripsy in treating calcified femoropopliteal arterial disease. Angiographic images were reviewed by core laboratory. The primary endpoint of safety is freedom from major adverse limb event (MALE) at 1 month. The primary effectiveness endpoint is acute procedural success, defined as achieving less or equal 30% mean residual narrowing postfinal treatment with no bailout stenting. A total of 29 consecutive patients were included (355-nm laser 15 patients [15 vessels] and Shockwave lithoplasty 14 patients [15 vessels]). At baseline, there were no differences between the two cohorts in demographics or clinical presentation. Also, there were no difference in total occlusions (33.3 vs. 33.3%), lesion length (median: 12.0 vs. 12.1 cm), presence of moderate to severe calcium (86.7 vs. 100%). At 30-day, there were no MALEs in both groups. There were no perforations, type D dissections, or distal embolization seen in both cohorts. Bailout stent was driven by a higher residual stenosis and was 35.7 vs. 13.3% in Shockwave versus laser, respectively ( p  = 0.215). At 30-day ankle-brachial indices were similar between the two groups (median: 0.9 vs. 1.09). Both Shockwave and 355-nm laser are effective and safe in calcified femoropopliteal lesions. A numerically higher rate of bailout stenting was seen with Shockwave lithoplasty.

Despite well-established childhood immunization programs in many high-income countries, vaccination series are often delayed or not completed. Gaps in vaccination coverage are more common among children from socioeconomically disadvantaged households, among whom they are associated with higher rates of related hospitalizations. We aimed to assess the extent of these gaps in Germany, as well as the presence of socioeconomic inequality and the factors accounting for it. Using health insurance claims data from Techniker Krankenkasse for 2016-2019, we examined vaccination coverage for a comprehensive set of STIKO-recommended childhood vaccinations in six birth-year cohorts (2011-2018; approximately 430,000 children; 2.5 million recommended vaccinations). Coverage was defined as completion of the recommended series with all doses administered within the recommended age window. Socioeconomic inequality was quantified using the Erreygers-corrected concentration index and decomposed into contributions from factors such as parental education and travel time to the treating physician. Approximately 80% of vaccination series in the sample were complete and administered within the recommended age window. Vaccination coverage showed a small but statistically significant socioeconomic gradient (concentration index = 0.024, 95% confidence interval: 0.023 to 0.025) favoring children from higher socioeconomic households. In the decomposition analysis, provider type accounted for the largest share of this gradient, with lower completion rates and timeliness among children whose outpatient care was mainly delivered by general practitioners compared with pediatricians. Parental education contributed to a lesser extent, and travel time contributed little to the observed inequality. Childhood vaccination coverage in Germany remains below national targets and shows a small socioeconomic gradient. The gradient appears to be less strongly related to logistical access barriers than to differences in how vaccinations are delivered in outpatient care outside pediatric settings. These provider-type differences in vaccination delivery may therefore be more relevant for narrowing the observed gradient than further reductions in travel time.

Metastatic involvement of the biliary tract and gastrointestinal (GI) system secondary to breast carcinoma is exceedingly rare. We hereby report a case of a 57-year-old woman with a past history of Human Epidermal Growth Factor Receptor 2-positive, estrogen and progesterone receptor-negative breast carcinoma treated 4 years earlier, who presented with jaundice, vomiting, early satiety, and significant weight loss. Biochemical evaluation revealed a cholestatic pattern of jaundice. Magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography revealed intrahepatic biliary dilatation secondary to a mass at the porta hepatis compressing the distal common bile duct, along with significant narrowing of the D1-D2 segment of duodenum. Endoscopic ultrasound-guided biopsy confirmed metastatic adenocarcinoma consistent with a breast primary. Due to anatomical constraints precluding endoscopic biliary stenting, the patient underwent palliative double bypass surgery of cholecystojejunostomy and gastrojejunostomy. Postoperatively, the patient demonstrated resolution of jaundice and restoration of normal oral intake, with marked symptomatic improvement. This case highlights a rare metastatic presentation of breast carcinoma closely mimicking primary hepato-pancreato-biliary malignancies, posing a significant diagnostic challenge. A high index of suspicion is thus essential in patients with a prior history of breast cancer presenting with biliary or upper GI symptoms. In cases where endoscopic interventions are not feasible, surgical double bypass proves to be an effective palliative strategy for symptom relief. RésuméL’atteinte métastatique des voies biliaires et du tractus gastro-intestinal secondaire à un carcinome mammaire est exceptionnelle. Nous rapportons le cas d’une patiente de 57 ans, ayant des antécédents de carcinome mammaire HER2 positif, négatif pour les récepteurs hormonaux, traité quatre ans auparavant, admise pour ictère, vomissements, satiété précoce et amaigrissement. Le bilan biologique objectivait un syndrome cholestatique. La cholangiopancréatographie par résonance magnétique et la tomodensitométrie abdominale avec contraste ont révélé une dilatation des voies biliaires intra-hépatiques secondaire à une masse du hile hépatique comprimant le cholédoque distal, associée à un rétrécissement du duodénum (D1–D2). La biopsie guidée par échoendoscopie a confirmé un adénocarcinome métastatique compatible avec une origine mammaire. En raison de contraintes anatomiques rendant impossible le drainage biliaire endoscopique, une dérivation palliative par double court-circuit (cholécystojéjunostomie et gastrojéjunostomie) a été réalisée. L’évolution postopératoire a été favorable, avec régression de l’ictère et reprise de l’alimentation orale. Ce cas illustre une présentation métastatique rare mimant une néoplasie hépato-pancréato-biliaire primitive, posant un défi diagnostique. Un haut niveau de suspicion est essentiel, et en l’absence d’alternative endoscopique, le double court-circuit chirurgical constitue une option palliative efficace.

To investigate the transport behavior of multiple particles in microchannels under ultrasonic actuation, a strongly coupled PD-IB-CLBM framework is developed in this work. In this framework, peridynamics (PD) is employed to describe the motion and deformation of solid particles, the cascaded lattice Boltzmann method (CLBM) is used to resolve the flow field, and the immersed boundary method (IBM) is adopted to enforce fluid-solid coupling. Based on this model, the migration dynamics of single and multiple particles in single-channel, parallel multi-channel, and T-shaped microchannels are systematically studied, with emphasis on the effects of particle number, channel geometry, and ultrasonic frequency on inlet capture, stable transport, and path selection. The results show that particle transport generally undergoes a transition from an initial oscillatory stage to a stable directional transport stage. Increasing particle number intensified inlet competition and trajectory disorder, potentially hindering the smooth entry of some particles. Parallel multi-channel structures enhance the capacity for simultaneous particle transport, but also introduce more pronounced local flow disturbances. In T-shaped channels, the transport behavior is highly sensitive to ultrasonic frequency. Among the tested conditions, 2 MHz achieves the best balance among capture range, flow stability, and transport consistency, whereas excessively high frequency (5 MHz) leads to an overly narrow effective capture region and deteriorates stable multi-particle transport. These findings reveal the coupled regulatory effects of ultrasonic frequency and channel geometry on collective particle transport, and provide theoretical guidance for ultrasound-assisted microfluidic manipulation and transdermal drug delivery systems.

Conventional thrombolytic agents exhibit significant limitations in treating thrombotic disorders characterized by narrow therapeutic windows and persistent vascular injury, failing to meet clinical requirements in terms of precision, timeliness, and treatment durability. To address these challenges, we have developed a blood cell membrane-camouflaged probiotic-powered micro-robot system (EcN-PN/rt-PA). This innovative system utilizes natural probiotics as biological carriers functionalized with drug-loaded hybrid membrane nanovesicles possessing dual-targeting capabilities against thrombus. By harnessing the rapid motility of probiotics and the active targeting properties of the hybrid membranes, the system achieves rapid and precise delivery of thrombolytic drugs to thrombotic tissues. Capitalizing on the innate rod-shaped structure and self-propelling capacity of probiotics, this micro-robot demonstrates enhanced penetration depth into thrombotic tissues, significantly improving thrombolytic efficiency. Experimental results reveal that this thrombolytic micro-robot, which combines thrombus targeting, deep penetration, and prolonged circulation characteristics, not only rapidly and accurately targets and penetrates thrombotic tissues but also extends the biological half-life of thrombolytic drugs approximately 193-fold, enabling sustained thrombolytic effects while effectively inhibiting secondary thrombus formation. This novel dual-targeting thrombolytic strategy provides an important scientific solution for treating thrombotic diseases with narrow therapeutic windows caused by vascular injury.

Recent shifts in the geopolitical landscape, including the threat of nuclear conflict and the proliferation of nuclear materials, have heightened concerns about radiological emergencies. Acute radiation syndrome (ARS) is a major health consequence of such events, but effective medical countermeasures (MCMs) remain limited. Although several compounds have been approved as mitigators to treat ARS, there is currently no FDA-approved drug that can be used as a prophylaxis-administered before exposure to prevent or lessen the effects of radiation. One key mitigator is Nplate (romiplostim), a thrombopoietin receptor agonist currently approved for use as soon as possible after expected or confirmed exposure to myelosuppressive doses of radiation (2 Gray (Gy)). However, there is growing interest in expanding its utility beyond this narrow window. Our current research suggests that administering Nplate at later time points (e.g., 48 or 72 hours postexposure) could still provide a significant survival benefit. Furthermore, its potential as a prophylaxis is being explored, which could offer a vital layer of protection for first responders and military personnel in high-risk environments. This expansion would address a critical gap in current medical readiness and increase resilience in a radiologically contaminated environment. The efficacy of Nplate as both a mitigator and prophylaxis for ARS was evaluated in 2 separate studies using C57BL/6 mice. The first study used the Armed Forces Radiobiology Research Institute (AFRRI) cobalt-60 gamma irradiator to simulate nuclear fallout. Nplate was administered as a mitigator at 24, 48, and 72 hours postirradiation and as a prophylaxis at 6 and 12 hour preirradiation. The second study utilized the AFRRI Training, Research, Isotope, General Atomic (TRIGA) reactor to mimic nuclear detonation with mixed neutron-gamma radiation. All experiments were conducted under the oversight of the Uniformed Services University of the Health Sciences (USUHS) Institutional Animal Care and Use Committee (IACUC). When used as a mitigator for delayed administration, Nplate significantly enhanced the survival of both male and female subjects in a dose-dependent manner. In addition to improved survival rates, Nplate treatment led to the recovery of deficiencies in blood cell counts, an increase in colony-forming units (CFUs) in bone marrow, and a notable increase in megakaryocytes in sternal sections. Similarly, and even more pronounced, results were seen when Nplate was used as a prophylaxis. Prophylactic use resulted in a greater increase in overall survival, underscoring its potential to protect against the damaging effects of radiation. The data presented in this manuscript provides compelling evidence to support the expanded use of Nplate as a MCM against radiation exposure. Our findings demonstrate that Nplate's efficacy extends beyond its current approved use, remaining effective as a mitigator when administered at 24, 48, and even 72 hours postirradiation. Furthermore, the studies show that Nplate is a potent prophylaxis, offering significant protection for military personnel and first responders in the event of a radiological or nuclear incident. This data will be used to support continued interactions with the FDA to broaden Nplate's indications.

Rapid functional discovery increasingly demands synthetic methods that are compatible with automation, high-throughput experimentation, and minimal operational complexity. Miniaturized parallel synthesis in multi-well microplates provides a compelling alternative to traditional combinatorial approaches, enabling streamlined workflows and direct biological testing of crude products without purification. However, synthetic strategies suitable for such direct-to-biology applications remain largely confined to a narrow set of crosslinking reactions, limiting access to complex, three-dimensional scaffolds central to drug discovery. Herein, we report a highly efficient and broadly applicable multicomponent cyclocondensation that enables the rapid, modular construction of multisubstituted 6-membered tetrahydrotriazine scaffolds from readily available aldehydes, amines, and hydrazines through simple mixing at room temperature. The reaction proceeds cleanly under mild conditions and is fully compatible with plate-based synthesis, allowing high-purity compound libraries to be generated and evaluated directly upon solvent removal. Using this "mixing-drying-biotesting" workflow, we rapidly constructed and screened pilot 1,3,5-tri-substituted tetrahydrotriazine libraries with diverse structures, leading to the identification of potent α1A-adrenoceptor antagonists. Together, this work demonstrates how the integration of novel synthetic chemistry with direct-to-biology screening can unlock previously unexplored heterocyclic chemical space and accelerate early-stage drug discovery, while reducing the time, cost, and experimental waste.

For a long time, milk fat has been recognized as a potential risk factor in the diet for cardiovascular disease because of its high saturated fatty acid content. However, mounting evidence may call into question this narrow-minded view, as it does not account for the complex and at times paradoxical relationship between dairy consumption and health. This review suggests that an integrative approach should be adopted to re-evaluate the health benefits of milk fat. We suggest that milk fat should not be viewed from a solely "saturated fat" perspective and should be considered a four-dimensional system: functional lipid diversity, food matrix structure, dose-response relationship, and individual metabolic characteristics. We first call attention to the fact that milk fat is not simplified in its fatty acid classifications and thus is molecularly heterogeneous. Second, we will discuss the modulation of lipid digestion kinetics and metabolic fate by the food matrix. Third, we combine epidemiological evidence, which shows the different kinds of nonlinear dose-response relationships between dairy consumption and health outcomes. Fourth, we discuss the contribution of genetic background, gut microbiota, and metabolic status to interindividual variability in response to milk fat. Finally, we discuss the implications of this framework for dietary guidelines, clinical practice, and innovation of dairy products. The change in paradigm from a single "saturated fat" to a multidimensional approach resolves inconsistencies that plagued the single "saturated fat" paradigm and offers a scientific playing field for personalized nutrition and precision dietary recommendations.

The phylum Brachiopoda, which originated in the Cambrian, includes the most diverse subphylum Rhynchonelliformea, comprising the three extant orders: Thecideida, Terebratulida, and Rhynchonellida. These animals possess a calcitic bivalve shell secreted by the mantle. Despite the long evolutionary history of brachiopods, the biomineralization processes in rhynchonelliforms remain poorly characterized. In this paper, we review published data on shell properties (morphology, microstructure, and chemistry) and mantle biology (ultrastructure, ontogeny, and molecular mechanisms) to propose a comprehensive hypothesis for their biomineralization process. We propose that shell secretion in rhynchonelliforms involves a conserved molecular mechanism shared with other carbonate-skeleton-producing animals. Furthermore, we suggest an ontogenetic model based on a cellular "conveyor belt" mechanism of shell secretion. The extremely narrow privileged space, together with the tight spatial association between secondary-layer fibers and the cells of the outer mantle epithelium, indicates an exceptionally high degree of cellular control over shell growth. This precise control likely underpinned the evolution of the remarkably complex skeletal support of the lophophore in rhynchonelliform brachiopods. This apomorphic trait probably played a key role in the evolutionary success of these animals, enabling them to achieve the highest diversity and ecological dominance within the phylum.

Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. To examine two‑decade trends in sex‑stratified mortality from preterm birth complications using standardized equity indicators. We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2. Main findings: Mortality from preterm birth complications fell substantially in Sierra Leone between 2001 and 2021, but male neonates consistently experienced about 20–25% higher mortality than females.Added knowledge: This is the first two-decade, sex-stratified analysis of preterm mortality in Sierra Leone using standardized WHO equity metrics, revealing a persistent male disadvantage that remained stable despite overall survival gains.Global health impact for policy and action: Routine sex-disaggregated monitoring and sex-sensitive neonatal care protocols are essential to ensure that progress toward SDG 3.2 is equitable and does not leave male preterm infants behind.

Plant-derived exosome-like nanovesicles (PDENs) have recently gained prominence as biocompatible, renewable nanocarriers, but lipid-dense tropical plants remain an underutilized vesicle reservoir and present substantial hurdles for efficient isolation. Here, we establish Pandanus conoideus (red fruit), a Papuan endemic with unusually high carotenoid, tocopherol, and unsaturated fatty acid content, as a new source of PDENs and develop a matrix-adapted polyethylene glycol (PEG 6000) workflow for their scalable isolation from fresh fruit (RFF), dried simplicia (RFS), and long-stored red fruit oil (RFO). Differential centrifugation coupled with matrix-specific PEG precipitation and syringe filtration yielded RFO-derived PDENs (RFO-PDENs) with exosome-like hydrodynamic diameters (predominantly 30-150 nm by nanoparticle tracking analysis), low polydispersity, and spherical, bilayered morphology by transmission electron microscopy, whereas RFF and RFS favored larger, more polydisperse vesicle/aggregate populations. Optimization uncovered narrow matrix-dependent PEG "windows", with 8-10% PEG producing the most homogeneous, highly concentrated RFO-PDENs fraction (up to 1.2 × 1010 particles/mL) using only benchtop equipment, thus enabling straightforward scale-up. Untargeted LC-HRMS metabolomics of bulk RF-PDEN preparations revealed a complex metabolite landscape dominated by fatty acids and oxylipins, fatty acid amides, sphingolipids/ceramides, amino acids, and cyclic peptides, together with signature P. conoideus antioxidants (α-tocopherol, α/β-carotene) and dermatologically relevant metabolites such as azelaic acid. However, the presence of highly abundant signals with plausible nonendogenous or process-related origins (e.g., 4-undecylbenzenesulfonic acid) indicates that these data represent a composite PDENs preparation rather than a definitive catalog of enclosed vesicular cargo, and potential coprecipitation of matrix- or process-derived components cannot be excluded. Complementary label-free proteomics identified a low-complexity proteome enriched in plastid/mitochondrial ribosomal proteins, Cytochrome b 6f complex subunit VI, and a dense cohort of lectin and lectin receptor-like kinases that is consistent with translation/redox-associated components and a lectin-enriched, signaling-candidate vesicle surface, while remaining preliminary and qualitative in nature. Collectively, these findings show that matrix-optimized PEG precipitation enables isolation of a high-yield RF-PDEN reservoir from challenging, lipid-rich red fruit oil with preserved membrane architecture and a composition consistent with bioactive lipid and antioxidant enrichment, while underscoring that proposed antioxidant, anti-inflammatory, barrier-repair, or depigmenting applications of RFO-PDENs remain hypothesis-generating and will require future functional validation.

Phenytoin is a highly protein-bound medication and monitored due to its narrow therapeutic range. Free phenytoin serum concentratinos (fPHTm) are not readily available in many institutions. To evaluate whether population-specific correction factors (CFs) improve estimated free phenytoin serum concentrations (fPHTe) compared with traditional Winter-Tozer CF. This retrospective review included adults with same-day measured total phenytoin serum concentrations (mPHT), fPHTm, albumin, and blood urea nitrogen (BUN) values. Patients were stratified by active/breakthrough seizures, intermittent hemodialysis (IHD), or adults younger than 65. Patient-specific fPHTm percentages were used in the estimation of fPHTe. Of 126 phenytoin levels reviewed, 66 met inclusion criteria. Population-specific CFs demonstrated lower bias and greater precision. In patients with active/breakthrough seizures and BUN <50 mg/dL, CF 0.29 improved accuracy compared with CF 0.2 (reduced mean percentage error [MPE] -59.59 vs -111.99 - indicating overprediction, root mean square error [RMSE] 1.79 vs 2.91), with similar trends when BUN exceeded 50 g/dL. A preliminary finding among adult patients younger than 65 showed better performance with a CF 0.275 than CF 0.2, with lower MPE (-40.43 vs -78.98) and RMSE (1.32 vs 2.16). In the IHD cohort, CF 0.201 outperformed CF 0.1 (MPE -74.40 vs -197.53 and RMSE 2.07 vs 5.32). Population-specific CF estimated fPHTe more accurately and precisely than traditional CF. Findings remain preliminary due to limited representation, and further research is needed to improve CF selection across various subgroups.