搜索结果：Allowed

Background In ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus, optimal trepanation sites and trajectories are critical to prevent shunt malposition. However, the effect of cerebral sulci at the burr hole site on unexpected intraoperative entry point changes remains unclear. Methods Preoperative computed tomography data from 50 patients with idiopathic normal pressure hydrocephalus (January 2018 to September 2024) were retrospectively reviewed. We analyzed the frequency of cerebral sulci beneath Kocher's point necessitating entry point shifts and the distribution of alternative sites. Shunt malposition rates were compared between navigation-guided puncture on the basis of preoperative simulation and a conventional cohort using surface anatomical landmarks. Results Radiological evaluation of 100 bilateral Kocher's points predicted minor puncture site adjustments in 20% of patients and major modifications, such as burr hole enlargement or relocation, were predicted in 17% of patients. In the conventional technique, the incidence of hemorrhage along the catheter tract was 7.4%, and the rate of suboptimal catheter tip placement was 33%. Introduction of a navigation system allowed preoperative identification of entry point shifts and trajectory planning. Consequently, no catheter tract hemorrhages occurred, and the rate of suboptimal placement was reduced to 13.0%. Conclusion Unanticipated cerebral sulci at conventional entry points are negative confounding factors for successful ventricular puncture. Preoperative identification of appropriate entry points and trajectories is important for surgical success. Recognizing such anatomical variations through preoperative review of standard radiological images is essential for improving accuracy and safety, even when technological aids are limited. Furthermore, the implementation of a navigation system provides critical support in achieving these objectives and reducing malposition rates.

Persistent organic pollutants (POPs) are an environmental challenge and a health hazard because of their persistence, bioaccumulation, toxicity, and long-range transport. The use of sapropelic sludge in medicine requires that water and sludge samples are free of pesticide residues and that their content complies with regulatory requirements. Gas chromatography with an electron capture detector (GC-ECD) was used for the preliminary screening of water and sludge of Techirghiol Lake for POPs (polychlorinated biphenyls). Slight contamination with polychlorinated biphenyl compounds is observed in both the lake water and the sludge, which may have negative effects on human health. Regarding organochlorine pesticides, significant concentrations were found in the water from Techirghiol Lake, while their concentration in the sludge was found within the limits established by the national authorities (smaller concentrations than 0.1 µg L-1 are allowed by the national authorities), except for lindane and aldrin, for which the concentrations exceeded by far 0.1 µg L-1.

There are several somatic techniques for reducing anxiety through relaxation, i.e., the reduction of tension. Tension is an important component and corresponds, in the primordial mechanism of fear, to the pre-encounter immobilizing alert state of the defense cascade. It is hypothesized that an energetic generalized muscular activation, such as that used to face a fighting (circa-strike), can correct the immobilizing tension and counteract anxiety. To evaluate the degree of effectiveness against anxiety and anxiety attacks of a technique based on a phase of sustained, generalized muscular activation followed by relaxation. During a private outpatient clinical practice, selected subjects suffering from various anxiety disorders were offered the opportunity to try a technique for controlling anxiety attacks. They were instructed to activate a generalized isometric sustained contraction in apnea (GISCA), followed by a generalized relaxation (GISCA+relax), to be implemented as needed during an anxiety attack. The subjects were asked to apply the maneuver in alternation, in different episodes, with a generalized relaxation. They were asked to evaluate, after repeated use, the following aspects: a) whether GISCA+relax helped in controlling anxiety, b) if the addition of the GISCA phase was more effective than generalized relaxation alone, and c) if the GISCA phase facilitated the acquisition of the subsequent generalized relaxation. The results concern the first 20 patients who were allowed a complete evaluation. A substantial majority of them (75%) reported that the complete maneuver (GISCA+relax) helped in controlling anxiety and anxiety attacks, and that was more effective than generalized relaxation alone and facilitated its acquisition. Compared to relaxation techniques, GISCA+relax offers the advantage of easier application in acute situations, such as during an anxiety attack or in anticipation of anxiety-provoking events (e.g., performance anxiety). However, a sustained generalized contraction is physical exercise, with the positive effects of any non-traumatic physical activity on health-related fitness. These first data, although on a limited number of patients, suggest that the proposed maneuver can help control anxiety. This new somatic behavioral approach likely counteracts anxiety by activating a primordial defense mechanism. Since it can be acquired by patients with sufficient simplicity, it is suggested that it could be considered an alternative to other somatic techniques or the use of as-needed medications.

Inventorying biodiversity in reserves is a routine activity in conservation, yet for hyper-diverse insect groups such as macro-moths, general ecological patterns remain underexplored. We collated and analysed macro-moths (Lepidoptera) inventories from 292 nature reserves across the Czech Republic, encompassing 941 species. Inventories varied in surveying effort and methodology but collectively allowed examination of factors influencing moths' species richness, assemblages' composition and their associations with the species' traits. Species richness increased with elevational scope and was highest in reserves covering steppes and mesic grasslands. Geographic position of the reserves, altitude and elevational scope affected the moth assemblages' composition. Reserves at low altitudes hosted larger moths forming multiple generations and developing on forbs, whereas high-altitude reserves hosted species developing on shrubs and trees, forming fewer generations, overwintering in later stages and inhabiting broader habitat and altitude ranges. Regional biogeography also affected the assemblages, with Carpatho-Pannonian reserves supporting large-winged habitat-specialists, often overwintering in early developmental stages. Our results demonstrate that even heterogeneous data can reveal consistent patterns when interpreted through species' traits. These findings demonstrate the value of reserve inventories compiled by dedicated amateur lepidopterists for deciding on reserve management strategies and identifying key habitats for species of conservation concern.

Since the turn of the century, long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) have played a major role in malaria control. However, the effectiveness of these tools is declining due to the development of insecticide resistance and other factors, creating an urgent need for complementary strategies. Larval source management (LSM), through the application of biological larvicides or the autodissemination of larvicides by ovipositing female mosquitoes, offers alternative avenues to target malaria vectors. Predicting the effectiveness of such approaches requires a detailed understanding of oviposition site selection behaviour in female Anopheles gambiae sensu lato. This study investigated the oviposition strategy of female Anopheles arabiensis in relation to aquatic habitat size under semi-field conditions in south-central Tanzania. An array of twelve alternating small (30 cm diameter, 20 L capacity) and large (60 cm diameter, 40 L capacity) artificial larval habitats was established in two compartments of a semi-field system. In quadruplicated experiments, forty wild gravid An. arabiensis females were released into each compartment and allowed to oviposit in their preferred habitats. The resulting third-instar larvae were collected, counted and preserved in ethanol. Larvae from one replicate were subjected to DNA extraction and microsatellite genotyping. Sibship analysis using Bayesian-likelihood methods (COLONY software) was conducted to reconstruct individual female oviposition behaviour. Rather than distributing eggs in proportion to habitat size, An. arabiensis females significantly preferred smaller habitats. Sibship analysis showed that 49.2% of females skip-oviposited across two to four habitats, while others deposited eggs in only one. Skip-ovipositing females laid more eggs overall, but fewer eggs per habitat, and were more likely to alternate between small and large habitats than to use habitats of the same size, consistent with a potential bet-hedging strategy. Gravid An. arabiensis females exhibited a strong preference for smaller aquatic habitats and frequently engaged in skip-oviposition. These behavioural traits have potential implications for optimising larval-stage vector control tools, particularly those based on autodissemination and attract-and-kill strategies.

Density functional theory (DFT) and time-dependent density functional theory (TDDFT) have been employed to study the plasmonic coupling effects of silver, gold, and copper clusters supported on titania. The adsorption of metal nanoparticles on the surface of rutile TiO2 changes the electronic properties of the system, resulting in the disappearance of the TiO2 bandgap. The analysis of photoabsorption spectra allowed us to identify surface plasmons and quantify their contribution to the absorption of visible light. Using specific analysis tools, we evaluated the strength of the plasmonic coupling between metal nanoparticles and TiO2, allowing the identification of favorable configurations for the plasmonic coupling.

Does dispersal differ between the sexes? This question, anchored in a body of rich theoretical literature, has received little empirical attention in marine invertebrates. Yet, dispersal is a key ecological process with profound implications for species management and conservation. In this study, we investigated sex-biased dispersal in the European spiny lobster (Palinurus elephas) by sampling females and males from six marine reserves and their surroundings in the northwestern Mediterranean. By genotyping 180 individuals at 8390 markers, we found that both sexes exhibited panmixia. Genetic differentiation estimates did not differ significantly between sexes, despite a tendency toward slightly higher and more geographically structured estimates in females. Additionally, we identified 72 sex-linked markers with significant differences in heterozygosity between females (fully heterozygote) and males (fully homozygote). These markers not only allowed the sex assignment of 61 individuals of unknown sex but also provided the first evidence for a ZZ/ZW sex determination system in P. elephas. Beyond their fundamental insights, these sex-linked markers hold strong applied potential for species management, particularly in fisheries where sex-specific regulations exist. Our findings underscore the power of genomic markers to study sex-biased dispersal, elucidate sex determination systems, and facilitate sex assignment, with important implications for species conservation and management.

The rise of Klebsiella pneumoniae (KP) and carbapenem-resistant KP (CRKP) poses grave threats to public health and food safety, creating an urgent demand for rapid point-of-care testing (POCT). Traditional detection methods are limited by laboratory barriers, making them unsuitable for POCT implementation. Herein, a one-tube assay integrating recombinant polymerase amplification (RPA) with CRISPR/Cas12a technology was developed for the rapid, sensitive and specific detection of KP and blaOXA-48-carrying CRKP. Specific primers targeting the KP-specific rpoB gene and carbapenem-resistance gene blaOXA-48 were designed, and optimal primer pairs were screened via agarose gel electrophoresis. CrRNA sequences were designed according to RPA amplicons, and the components of the CRISPR/Cas12a reaction were optimized. A two-step reaction system was initially evaluated, followed by the establishment of an integrated one-tube RPA-CRISPR/Cas12a assay. A total of 66 clinical specimens and artificially contaminated food samples were used for method validation, with microbial culture and qPCR as reference methods. The two-step assay was capable of detecting bacterial suspensions at a concentration of 100 CFU/mL. The one-tube system could be completed within 1 hour at 37 °C. This assay avoided aerosol contamination and allowed visual result readout under blue light. In the validation test, the detection results of the one-tube assay were consistent with those obtained by microbial culture and qPCR. This study constructed a dual-target RPA-CRISPR/Cas12a platform for the visual detection of KP and blaOXA-48-positive CRKP under blue light. This assay reduces reliance on sophisticated equipment and professional personnel. It can serve as a promising POCT tool for clinical diagnosis and food safety surveillance, and provides evidence for the timely formulation of rational antimicrobial treatment strategies.

Innovating in paediatric healthcare requires more than technological advancements; it demands meaningful collaboration with children and young people (CYP) and their families. This practice-focused paper demonstrates how co-creation can be embedded within paediatric medical device development by applying a rights-based approach to guide and inform the involvement activities. Drawing on three illustrative case studies from the National Institute for Health and Care Research (NIHR) HealthTech Research Centre in Paediatrics and Child Health (HRC-PCH), we show how CYP and their families contributed at various stages of innovation, from early concept development to prototype refinement. Each case is examined using Lundy's Model of Participation and the 3Ps framework (Provision, Protection, and Participation), allowing us to identify practical enablers and barriers to inclusive, ethical, and rights-based involvement. The cases highlight how co-creation can enhance the relevance, usability, and acceptability of paediatric medical technologies while fostering trust, equity, and empowerment among participants. We conclude by outlining actionable, practice-based recommendations for embedding CYP and family involvement within the culture, governance, and day-to-day processes of paediatric innovation. This offers a practical roadmap for teams engaged in research, healthcare, and industry.

Immune checkpoint inhibitors have transformed the landscape of cancer therapy; however, the challenge that most patients do not achieve durable benefits urgently necessitates the development of new strategies that extend beyond mere T-cell activation. mRNA processing-comprising alternative splicing, RNA modifications, and RNA editing-establishes a dynamically regulated connection between the intrinsic characteristics of tumors and anti-tumor immunity. This review systematically summarizes how mechanistic insights into these processes can be translated into concrete approaches that enhance the precision of immunotherapy. We first outline how the widely dysregulated splicing events in tumor cells produce abundant neoantigens at a frequency that significantly exceeds that of gene mutations. A subset of these splice isoforms is shared among patients, offering a unique antigen resource for the development of 'off-the-shelf' mRNA vaccines, thereby circumventing the manufacturing bottleneck associated with personalized vaccines. Concurrently, RNA modifications driven by N6-methyladenosine (m6A) create an immunosuppressive network at the epitranscriptomics level by bidirectionally modulating the stability of immune checkpoint molecules, e.g., Programmed Death-Ligand 1 (PD-L1), and the functional polarization of macrophages and dendritic cells. In parallel, Adenosine Deaminase Acting on RNA 1 (ADAR1)-mediated Adenosine-to-Inosine (A-to-I) editing designates endogenous double-stranded RNA as 'self,' allowing tumors to evade innate immune surveillance and conceal 'non-self' signals. This includes the exploitation of splicing-derived neoantigens for designing personalized or shared mRNA vaccines, the deployment of small-molecule inhibitors targeting FTO, Methyltransferase Like 3 (METTL3), and YTH Domain Family Member 2 (YTHDF2) to alleviate immunosuppression, and the utilization of antisense oligonucleotides to precisely modulate splicing factor activity, thereby reversing T-cell exhaustion. Building on this foundation, the combination of these strategies with immune checkpoint blockade has already demonstrated clear synergistic effects in preclinical models and early-phase trials. Additionally, biomarkers based on splicing signatures and expression levels of modification enzymes show promise for accurately stratifying benefiting populations. Despite challenges such as off-target toxicity, intratumoral heterogeneity, and delivery technologies, cutting-edge tools like single-cell and long-read sequencing are rapidly bridging the translational gap. Strategies targeting mRNA processing are advancing cancer immunotherapy from a model of "broad-spectrum activation" to a new paradigm of "precision modulation."

Searching for objects in their surrounding is challenging for blind and visually impaired individuals (BVI) in daily life. Current assistive technologies powered by large language models (LLMs) and vision language models (VLMs) can offer BVI scene descriptions through conversations. However, communication is often inefficient in helping BVI to reach daily objects or destinations, because those general purpose LLMs/VLMs are not optimized for interpreting or conveying spatial information. We developed a smart glass solution that can utilize open vocabulary object detection models to aid BVI in searching/reaching for a variety of specific objects that are not limited to fixed categories of model training. In our implementations, video streams from the glasses can be processed using open vocabulary object detection models either locally or on other connected devices, such as a smartphone or computer. User can input custom search prompt verbally. This hands-free solution allows people to naturally scan their surroundings by moving their heads, and the stereo audio tones provide directional cues in horizontal and vertical directions to help zero in on the targets, so that it becomes possible to reach these objects accurately. We conducted a human subject pilot study involving 5 blindfolded individuals who reached specific objects (e.g. grabbing the red bottle; reaching the empty chair) among other distractors. The smart glasses solution was compared with Ray-Ban Meta glasses that were running built-in Meta AI for scene recognition. The average task time with our solution (53 seconds) was significantly lower than Meta glasses (126 seconds, p<0.001). The device was also demonstrated to successfully aid a blind user in a grocery shopping scenario. This work shows that active orientation guidance, which is typically lacking in VLMs but provided by our smart glasses solution, can aid in interaction with surrounding environment, such as when reaching for objects and destinations.

Wellness tourism is among the fastest-growing segments of the global health economy, yet its development in Central Asian heritage regions remains constrained by fragmented service delivery, limited digital infrastructure, and a shortage of evidence-based planning tools. In this Perspective, we argue that advancing wellness tourism in such regions requires coupling econometric diagnosis of revenue drivers with the design of a digital platform that operationalizes those drivers, and we illustrate this dual approach using Bukhara, Uzbekistan-a UNESCO World Heritage Site rich in thermal springs, therapeutic hot sands, and mineral-rich muds. Drawing on panel data from 12 wellness facilities observed over 2021-2024, a weighted least squares model identifies three revenue determinants: client base size, service breadth, and qualified staffing. Client base expansion and qualified staffing emerge as the strongest positive determinants, while service breadth shows a paradoxical negative effect, suggesting that resource dispersion outweighs portfolio benefits in this setting. Revenue projections indicate substantial sectoral growth by 2030, with nature-oriented sanatoriums leading in relative terms. Building on these patterns, we propose the "Wellness Bukhara Voucher System"-a digitally integrated platform connecting disparate facilities through standardized vouchers, QR-code authentication, automated analytics, and a public-private partnership financial model. The platform addresses the diversification paradox through "network specialization," allowing each facility to deepen its core competencies while the system as a whole expands service breadth via cross-referrals. We discuss infrastructure, stakeholder, regulatory, and privacy conditions for viable deployment, and argue that this perspective offers a transferable model for heritage regions seeking to convert natural healing assets into digitally coordinated wellness economies.

Deep learning methods for protein structure generation, sequence design, and structure and property prediction have created unprecedented opportunities for protein engineering and drug discovery. However, using these tools often requires navigating incompatible software environments, diverse input/output formats, and high-performance computing infrastructure, any of which may hinder adoption by primarily experimental chemical biology laboratories. Here, we present BioPipelines, an open-source Python framework that allows researchers to define multistep computational design workflows in a few lines of code. Additionally, its robust yet modular architecture provides a straightforward way to expand the tool kit with different functionalities, particularly by leveraging coding agents, with little effort. The framework currently integrates over 40 tools encompassing structure generation, sequence design, structure prediction, compound screening, and analysis. The same workflow code can be prototyped interactively in a Jupyter notebook and then submitted for production-scale runs without modification. We demonstrate applications in inverse folding, gene synthesis, de novo protein design, compound library screening, iterative binding site optimization, and fusion-protein linker optimization. We hope that this framework will empower researchers, allowing them to focus on the scientific question rather than computational logistics. BioPipelines is available under the MIT license at https://github.com/locbp-uzh/biopipelines.

Distal renal tubular acidosis (dRTA) is a rare disorder characterized by normal anion gap metabolic acidosis and hypokalaemia. Physiological changes during pregnancy may aggravate acid-base imbalance and influence foetal outcomes. A 40-year-old pregnant woman at 24-25 weeks of gestation presented with recurrent hypokalaemia and lower limb weakness. Laboratory findings showed normal anion gap metabolic acidosis, consistent with dRTA. The patient was treated with oral potassium supplementation and intravenous sodium bicarbonate, resulting in clinical improvement. In the third trimester, intrauterine growth restriction was identified. Delivery at term resulted in a live neonate with low birth weight.A literature review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines using PubMed, ScienceDirect, Wiley Online Library, SpringerLink, and ResearchGate for studies published between 2016 and 2026. Ten case reports met the inclusion criteria. Distal RTA was the most frequently reported subtype, accounting for 80% of cases. Most cases (70%) were first diagnosed during pregnancy. The most common treatment strategy was potassium supplementation combined with bicarbonate therapy (90%), administered either orally, intravenously, or as combination therapy. Adverse neonatal outcomes were reported in 50% of cases. Distal RTA should be considered in pregnant patients presenting with recurrent hypokalaemia and muscle weakness. Early recognition and appropriate correction of electrolyte imbalance and metabolic acidosis are essential to optimize maternal and foetal condition. Further studies are needed to better define clinical characteristics and management strategies of renal tubular acidosis during pregnancy. Vigilance is essential for rare distal renal tubular acidosis (dRTA)-pregnancy overlap As the leading form of RTA, (seen in 80% of reported cases), distal RTA (dRTA) frequently first appears during pregnancy (70% of instances), where it closely resembles routine hypokalaemic conditions. Clinicians should routinely check for anion-gap metabolic acidosis in pregnant women experiencing repeated muscle weakness, allowing timely treatment to avert severe maternal decline.Bicarbonate and potassium therapy boosts maternal-foetal success In this case, combined oral and intravenous replacement (effective in 90% of documented scenarios) quickly alleviated symptoms, yet the 50% chance of neonatal issues like intrauterine growth restriction or low birth weight underscores the approach's value for the foetus, providing internists with a reliable, safe strategy amid pregnancy's natural acid-base changes.Diagnostic pathway to reveal hidden dRTA dangers This experience arms internists with a straightforward algorithm (start with hypokalaemia evaluation, advance to acidosis testing) that cuts late-pregnancy risks, especially in settings with limited resources.

Glaucoma is the leading irreversible blinding eye disease worldwide and the global prevalence of glaucoma for individuals aged 40-80&#x202f;years is estimated as 3.54%. Early screening and prevention wherever possible are essential interventions of chronic disease management for glaucoma, but there is currently a lack of a recognized glaucoma screening model for Chinese population. Therefore, this study intends to construct and validate an artificial intelligence (AI)-assisted three-tiered glaucoma screening model based on the community population and assess its cost-effectiveness. This is a community population-based cluster randomized controlled trial with a minimum of 6-year follow-up. A three-tiered glaucoma screening strategy appropriate for Chinese individuals will be established, including a high-risk model questionnaire (primary screening), ophthalmic examinations (secondary screening, combined with physician-based and AI-assisted image interpretation), and definitive diagnosis by tertiary hospitals (tertiary screening). The participants of each community will be randomly divided into three groups (simple cluster randomization): no screening group, routine screening group, and tiered screening group. Participants in the no screening group will receive regular glaucoma-related health education, structured annual follow-up for symptom monitoring and recording of external ophthalmology visits, and a comprehensive ophthalmic screening at the end of the study to compensate for the absence of regular screening. A total of 28,275 participants (9,425 per group) will be recruited, allowing for an anticipated loss-to-follow-up rate of 20%. All primary outcome measures will be analyzed on a per-participant basis. The main endpoint is the glaucoma detection rate, with sensitivity and specificity of the screening as additional primary outcomes. Secondary outcomes involve comparative analyses of the cost-effectiveness of different screening strategies and the diagnostic accuracy of physician-based versus AI-assisted image interpretation. The protocol has been approved by the Biomedical Ethics Review Committee, West China Hospital of Sichuan University [2025(1021)]. All the participants will be required to afford signed informed consent. The study results will be presented at scientific meetings and published in a peer-reviewed journal. https://www.chictr.org.cn/showproj.html?proj=281642, identifier (ChiCTR2500107852).

Hydrogels with brilliant hydrophilicity and prominent biocompatibility are among the promising coating materials with engineering applications; however, they are still facing significant challenges in terms of multifunctional integration. Herein, inspired by loach, a multifunctional hydrogel with comprehensive advantages of lubricity, bacteriostasis, thermochromism, and antifouling property is successfully constructed by introducing loach mucus. The polyacrylamide/sodium hyaluronate (PAAm/HA) network was selected as the primary framework to provide fundamental mechanical properties. By replacing the water solvent with the extracted loach mucus, we can improve the mechanical property and achieve high lubricity and bacteriostasis of the hydrogel. The hydrogel exhibits a low friction coefficient in various solvent environments and has inhibitory effects on both Gram-negative and Gram-positive bacteria. Meanwhile, the hydrogel was proven to be antifouling. Furthermore, the inclusion of dopamine not only forms stable amide bonds with the carboxyl groups on HA but also serves as an adhesive moiety to allow the hydrogel to attach to diverse substrates, thus improving the hydrophilicity and lubrication of the target substrate. Besides, the crystallization properties of gluconate at low temperatures enable the hydrogel to undergo a thermochromic transparent-opaque transition. This work opens up an avenue for the rational design of multifunctional hydrogel coatings, which can be used for drag reduction in medical devices and privacy protection in smart windows.

Bilateral nephroblastoma, also known as Wilms tumor, represents a rare yet critical pediatric renal malignancy. Hypertensive emergencies with seizures are exceptional. We report the case of an 18-month-old girl who presented with status epilepticus secondary to malignant hypertension (180/120 mmHg) associated with a two-week history of abdominal distension. Clinical examination revealed bilateral lumbar masses, and computed tomography confirmed the presence of bilateral renal tumors, the largest measuring 102 &#xd7; 80 &#xd7; 100 mm. Neoadjuvant chemotherapy&#xa0;resulted in a partial response, with tumor size reduced to 69 &#xd7; 60 &#xd7; 63 mm, pending nephron-sparing surgery. Rapid diagnosis is crucial, as seizures presenting as the initial manifestation are rare and may delay recognition of the underlying abdominal pathology. Early imaging in cases of pediatric hypertension can prevent severe complications and improve outcomes, allowing renal preservation with survival rates exceeding 85%. Wilms tumor should be suspected in hypertensive toddlers presenting with abdominal signs, and prompt ultrasound evaluation is essential to avoid diagnostic delay and associated complications.

Cough is a common symptom associated with many mild and severe medical conditions such as acute and chronic respiratory disorders. However, it can also be linked to extrapulmonary pathologies such as gastroesophageal reflux. Whilst often beneficial in clearing secretions, a persistent dry cough can significantly impair quality of life and necessitate pharmacological intervention. Cloperastine, a non-opioid antitussive agent with central and peripheral mechanisms of action, is widely used in clinical practice. This narrative review critically examines the pharmacological properties, clinical efficacy and safety profile of cloperastine in the management of non-productive cough across adult and paediatric populations. In preclinical studies, cloperastine demonstrated antitussive efficacy 1.9 times greater than that of codeine, without narcotic effects. Moreover, cloperastine exhibits a quarter of the antihistaminic potency of diphenhydramine, does not impair mucociliary clearance and relaxes bronchial smooth muscle. Across more than 40 clinical studies, cloperastine was consistently effective in reducing cough frequency and intensity, with typical doses of 20-60 mg/day (hydrochloride) or 10-106 mg/day (fendizoate) in adults, and 6-106 mg/day (fendizoate) or 5-400 mg/day (hydrochloride) in children, where dosing was fixed or adjusted for age or weight. The onset of action was observed as early as 20 minutes. It demonstrated superior or comparable efficacy to codeine, clobutinol, dextromethorphan, levodropropizine, butamirate and dihydrocodeine. In paediatric populations, it improved sleep quality and sputum quality. Cloperastine is a well-tolerated and effective antitussive with a rapid onset, favourable safety profile and low risk of central nervous system side-effects, supporting its role as a valuable therapeutic option for dry cough across all ages. Cough is one of the most common reasons people visit a doctor, especially when it occurs in children. Cough can be productive (clearing mucus) or dry (no mucus). Dry cough often results from viral infections but can also be linked to conditions like asthma or reflux. In many cases, particularly in viral or post-viral infections, it may persist after the infection, disrupting sleep and daily life. Many medicines are available to treat dry cough but not all are effective or suitable for all patients. Some, such as the opioid codeine, work by suppressing the brain&#x2019;s cough reflex and may carry serious side effects such as drowsiness, nausea or even dependence, risks that are particularly concerning for children and older adults, who are more sensitive to such effects. Others, like levodropropizine, act only peripherally on the airways and, although safer, are considered less effective. Cloperastine is a non-opioid cough suppressant used for many years in several countries. It acts in two main ways: first, it acts on the brain&#x2019;s cough centre to reduce the urge to cough; second, it has peripheral effects, such as relaxing the muscles in the airways and exerting antihistaminic effects, reducing inflammation and irritation. Unlike many older cough medicines, cloperastine does not cause sedation or dependence and preserves the lungs&#x2019; natural ability to clear mucus. In this review, we looked at more than 40 clinical studies on the use of cloperastine in adults and children with dry cough. We found strong evidence that cloperastine is effective in reducing both the intensity and frequency of cough, with benefits noticeable within 20 30 minutes of taking the medicine. It also improved sleep quality, especially when a larger dose was given in the evening. A comparison against other established molecules is also included. What sets our review apart is its separate focus on paediatric and adult data. Many medical reviews focus only on adult patients, even though cough is extremely common in children and can cause significant distress for both the child and their caregivers. In the studies we analysed, cloperastine was shown to be safe and effective in children of all ages, including infants. It reduced nighttime coughing, helped children sleep better, and improved overall recovery while side effects were rare, mild, and temporary. Similar results were achieved in adults with acute or chronic cough, even when caused by serious underlying diseases. Another advantage of cloperastine is the variety of formulations, such as syrups, drops, tablets and chewable forms. This allows doctors to tailor the treatment to the patient&#x2019;s age, weight and preference, especially in children who may have difficulty swallowing pills. In conclusion, cloperastine is a well-tolerated, fast-acting and effective treatment for dry cough in both adults and children. Its unique dual mechanism, lack of sedative or narcotic effects, and favourable safety profile make it a valuable option for managing cough, particularly when symptoms interfere with daily life or sleep. Including children in the evidence base helps ensure that treatment decisions can be made with greater confidence across all age groups.

Clustering longitudinal data is challenging, particularly when measurements are high-dimensional, irregularly sampled, or noisy. We aim to provide a flexible and interpretable framework for identifying meaningful temporal subgroups and their key features. We introduce TAPIO, an ensemble-based clustering approach with longitudinal extensions, including longTAPIOtrajectories, longTAPIOsample, and longTAPIOMLD. These variants integrate dimension reduction and cluster-specific feature importance, allowing robust clustering of univariate and multivariate trajectories, as well as regularly and irregularly sampled longitudinal data. Simulation studies demonstrate that TAPIO accurately recovers cluster structure, identifies relevant features, and performs competitively with existing methods. longTAPIOtrajectories excels on regularly sampled data, while longTAPIOMLD outperforms alternatives for irregular measurements. Applications on a clinical cohort reveal patient subgroups with distinct survival patterns driven by key cardiac measures, and analyses of high-dimensional longitudinal proteomics data uncover molecularly distinct clusters with interpretable protein-level importance profiles. TAPIO offers a scalable, interpretable framework for longitudinal clustering that accommodates complex multivariate trajectories and high-dimensional data. Its ability to identify both meaningful clusters and their defining features has potential to advance patient stratification, biomarker discovery, and longitudinal data analysis in biomedical research.