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Candidate serum metabolite biomarkers of subclinical Haemonchus contortus infection in sheep

Bilateral collaborative streams with multi-modal attention network for accurate polyp segmentation

Condensate-mediated intracellular organelle sequestration

Correction: Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma

Energy efficient traffic data aggregation and routing for metropolitan optical access network

Screening autism spectrum disorder in children using machine learning on speech transcripts

Attention based unified architecture for Arabic text detection on traffic panels to advance autonomous navigation in natural scenes

Influence of geometry, reinforcement, and sterilisation on the dimensional accuracy of additively manufactured carbon fibre-reinforced nylon composites

Abstract Dimensional accuracy is a critical quality metric in manufacturing, particularly for medical devices subjected to sterilisation and disinfection. While additive manufacturing (AM), especially fused filament fabrication (FFF), facilitates the production of complex geometries, challenges such as void formation, surface deformation, and mechanical instability persist. This study evaluated the impact of sterilisation (autoclaving) and disinfection (ethanol) on the dimensional stability of 3D-printed carbon fibre-reinforced polymer (CFRP) parts. Two geometries – representing standard ASTM D3039 and complex non-standard designs – were printed using carbon fibre nylon-based composites with and without continuous carbon fibre (CCF) reinforcement. Dimensional accuracy and void fraction were assessed using micro-CT imaging and geometrical comparison analysis. While sterilisation (p = 0.247) and disinfection treatments (p > 0.05) had negligible overall effects on dimensional stability and void fraction, geometric design (p = 0.0036) and CCF inclusion (p = 0.0042) significantly influenced shape fidelity. The inclusion of CCF reinforcement enhanced resistance to deformation under external stressors, though its efficacy varied with design complexity. A significant interaction between geometry and CCF inclusion (p < 0.0001) demonstrated the dependency of void formation on design complexity and reinforcement. Additionally, maximum surface deviation was independently influenced by geometry (p = 0.0139) and CCF reinforcement (p = 1.1 × 10⁻⁴). This study highlights the strategic imperative of design optimisation and informed material selection to increase precision in additive manufacturing. By addressing the confluence of manufacturing constraints and stringent regulatory mandates, this research reinforces the viability of additive manufacturing for medical device fabrication, advocating for customised methodologies to harmonise functionality with compliance requirements.

Nonempirical models for assessing thermal properties of nonlinear triatomic molecules of the form XY₂

Investigating the universal character of k–M slope in earthquake catalogs from the Visibility Graph method

CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma

Cholangiocarcinoma (CCA) remains a lethal malignancy with limited therapeutic options. Through genome-wide CRISPR-Cas9 screening, we identified the adenosine triphosphatase (ATPase) valosin-containing protein (VCP) as a critical dependency in CCA. Compound screens revealed that the VCP inhibitor CB-5339 potently suppresses CCA proliferation in a panel of patient-derived organoids by inducing cellular senescence. It is known that senescent cells persist, and this can contribute to therapy resistance. To address this, we combined CB-5339 with senolytic agents (ABT-263 and conatumumab), which selectively eliminate senescent CCA cells, resulting in enhanced tumor suppression both in vitro and in vivo. Clinical analysis showed that VCP overexpression in CCA patients correlates with poor prognosis. Our study unveils a “one-two punch” strategy, targeting VCP-mediated senescence followed by senolytic clearance, offering a promising therapeutic approach for CCA.

Computational identification and evaluation of novel PD-L1 inhibitors for cancer immunotherapy

Pharmacokinetic profile of oral firocoxib in the koala (Phascolarctos cinereus)

The pharmacokinetic profile of firocoxib administered orally at 5 mg/kg as a single dose to three mature koalas of each sex is described. After single dose administration, the harmonic means for maximal plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2) were 79.2 ng/mL, 3.69 h, and 5.01 h, respectively. Males exhibited a higher Cmax than females (217.4 vs 48.4 ng/mL), suggesting greater oral absorption, while females had a slower elimination (t1/2: 5.87 h vs 4.38 h in males), however these sex differences were not significant. After a wash-out period, the same dose was administered every 12 h, on six occasions to the same koalas. With repeat dosing, females had higher trough concentrations at 24 and 48 h, and 12 h after the last dose, compared to the males. No observable adverse effects were evident in any of the koalas following repeat dosing. The target plasma concentration was approximately 100 ng/mL based on in vitro studies in other species to inhibit 80% of cyclooxygenase-2 activity (inhibitory concentration 80 [IC80]). During single firocoxib administration, this plasma concentration was attained only in the males and not in the females. Two unidentified metabolites were also observed in the chromatograms. Acknowledging the lipophilic nature of firocoxib and that it is therefore likely to persist in animals’ tissues longer than in plasma, firocoxib appears a useful nonsteroidal anti-inflammatory drug for the koala. The oral dose of 5 mg/kg twice a day for a maximum of six doses appears safe for mature male koalas. The data presented here suggests that mature females may require a higher dose (perhaps double the dose i.e., i.e., 10 mg/kg). Until further studies confirm the sex differences in pharmacokinetic profile of firocoxib and safety of higher doses in female koalas, a once daily administration of a higher dose is suggested.

Could dark energy be changing over time?

Computational investigation of LiMgZ half-heusler phases where Z = P, as, and Bi for optoelectronic and photoelectronic applications

Perceived family support and undernutrition among older outpatients of a Northern Nigerian hospital: A mixed methods study

Background Population ageing is increasing in developing countries like Nigeria, where declining death rates and high birth rates raise public health concerns, particularly regarding undernutrition. The shift toward nuclear family structures has diminished the support older adults receive from family members, compounded by economic challenges. This study seeks to explore the relationship between perceived family support and undernutrition among older adults, aiming to provide insights for enhancing health outcomes through improved family networks. Methods The sequential mixed-methods study (cross-sectional study of 145 older adults followed by in-depth interviews of the identified undernourished older adults) was conducted in the Geriatric unit of a General Outpatient Clinic in Kano. Inferential statistical analyses were used to determine the associations between family support and undernutrition. Thematic analysis of the text data from the interviews was done using Nvivo® version 12 pro. Results The mean age of respondents was 69.08 ± 7.82 (60–95) years; 76 (52.4%) were females. The prevalence of undernutrition was 15.2% and poor family support was 36.6%. Older age ≥ 75 (aOR=22.59, 95%CI = 5.45–93.57, P < 0.001), and poor family support (aOR=9.31, 95%CI = 2.32–37.42, P = 0.002) were the determinants of undernutrition in this study. Most undernourished older patients reported poor family interaction and satisfaction as the likely reasons for their condition. Conclusion This study reported a high prevalence of undernutrition, with older age and poor family support as significant determinants. Undernutrition, driven by poor family support, financial hardships and limited food variety, emerged as recurring themes in the qualitative arm.

Correction for Yeh et al., Three things we can do now to reduce the risk of avian influenza spillovers

Optimizing dietary protein and lipid levels for better growth performance, nutrient retention and flesh quality of grow-out striped catfish (Pangasianodon hypophthalmus)

Validity and clinical utility of a wrist-worn device against polysomnography

Objective Sleep-wearable technology has developed rapidly. However, few carried out validation in the real clinical settings. This study aimed to validate the performance of a consumer-grade sleep-tracking device compared to polysomnography (PSG) in participants from sleep clinics. Methods Participants referred to sleep clinic from 2021 to 2023 were recruited. Demographics and sleep questionnaires were also collected. All participants completed the PSG test in a sleep laboratory, along with a smart watch (HUAWEI WATCH GT2) that collected movement and heart rate signals using built-in sensors. Epoch-by-epoch agreement analysis and the Bland-Altman method were applied to evaluate the performance of smart watch. Results 98 participants were included in this study. 82 of them were men, with a mean age of 45.3 ± 10.6 years. The smart watch had a high sensitivity (95.9%), accuracy (87.3%), positive predictive value (72.2%), and relatively low specificity (47.9%) for sleep/wake performance. Sleep staging comparisons were mixed. Comparing to PSG, although smart watch tended to overestimate total sleep time (+28.7 min, P = 0.001), sleep efficiency (+5.94%, P < 0.001), sleep onset latency (+8.53 min, P < 0.001) and underestimate wake after sleep onset (−37.00 min, P < 0.001), acceptable agreement was observed in sleep/wake detection (Kappa coefficient>0.4), total sleep time and sleep efficiency (intraclass correlation coefficient>0.4). This agreement was less satisfactory in patients with OSA or insomnia. Conclusion This study compared the performance of a consumer-grade sleep-tracking device with that of PSG. The HUAWEI WATCH GT2 exhibited high agreement in sleep/wake detection. Such devices could be used as alternatives for successive sleep detection and could provide significant benefits to sleep hygiene with more advanced algorithms in the future.

Developing new technologies to protect ecosystems: Planning with adaptive management

Technology development is an essential investment for policymakers to address contemporary global crises, including climate change, biodiversity loss, the energy transition, and emergent infectious diseases. However, investing limited resources in the development of new technologies is risky. The research and development process is unpredictable, with unknown timelines and outcomes. In addition, even after successful development, the effects of deploying a new technology remain uncertain. When confronted with these uncertainties, policymakers must determine how long they should allocate resources to developing new technologies. Informed decisions require anticipating possible successes and failures of both technology development and deployment, which is a challenging optimization task when managing dynamic systems, such as threatened ecological systems. Using an adaptive management approach from AI, we find a time limit new technologies should be developed for, which balances costs, benefits, and uncertainties during development and deployment. We extract clear and transparent general rules for investing in new technologies, building on an analytical approximation. Using Australia’s Great Barrier Reef as a case study, we demonstrate that the development time limit ranges between 0 to 45 y before surrendering. We also show how characteristics of an ecological system influence the optimal investment strategy. Our approach can inform the development of new technologies in multiple domains including biodiversity conservation, public health, energy production, and the technology industry more broadly.