Bühler (United Kingdom)

Covering: January 2014-June 2025. Previous review: Natural Product Reports, 2014, 31, 1612Natural products (NPs) have long been foundational in medicine, from ancient herbal remedies to the discovery of transformative drugs like morphine and quinine. The mid-20th century marked a 'golden age' for antibiotic discovery from natural sources, which then expanded into other therapeutic areas. However, by the late 20th century, other technological advances had shifted NPs from being a central component of the discovery process to one of several options. This review explores the current role of NPs in pharmaceuticals by analysing NP-derived (NP-D) drugs approved since 2014 and clinical candidates in development as of the end of 2024. 58 NP-related drugs launched between January 2014 and June 2025 were identified, which included 45 NP and NP-D new chemical entities (NCEs) and 13 NP-antibody drug conjugates (NP-ADCs). Next, all 579 drugs-388 (67%) of which were NCEs and 191 (33%) were new biological entities (NBEs)-approved globally from 2014 to 2024 were analysed. In total, 56 (9.7%) of these 579 drugs were classified as NPs or NP-Ds using this review's NP definition: 44 NCEs (7.6% overall; 11.3% of NCEs) and 12 NP-ADCs (2.1% overall; 6.3% of NBEs). The number of new NP-D NCEs and NP-ADCs has fluctuated between 0 and 8 annually since 2014, with an average of five approvals per year. Next, 125 NP and NP-D compounds were identified that were undergoing clinical trials or in the registration phase at the end of December 2024. Thirty-three new pharmacophores not previously found in approved drugs are now in development; however, only one has been discovered in the past 15 years. This review highlights the enduring promise of NPs, despite their diminished role in drug discovery, and advocates for renewed emphasis on bioassay-guided isolation and mode of action studies to identify new drug leads.

The intrinsic soft nature of compliant supernumerary limbs and exosuits makes them appealing candidates for assisting human movements, with potential applications in healthcare, human augmentation, and logistics. In the following chapter, we describe the technology used in exosuits and supernumerary limbs for assistance with activities of daily living, with emphasis on aiding grasping and flexion/extension of the elbow joint. We discuss the mechanical design principles of such devices, detail the control paradigms that can be used for intention-detection, and present the design and evaluation of cutaneous interfaces used for force feedback rendering. Tests on healthy and impaired subjects highlight that exosuits and supernumerary limbs are potential cost-effective and intrinsically safe solutions for increasing the capabilities of healthy subjects and improving the quality of life of subjects suffering from motor disorders.

Bu çalışma, Kingdon’ın Çoklu Akışlar Teorisi çerçevesinde dijital dönüşüm, yeşil dönüşüm ve çok kutuplu jeopolitik düzen gibi çağdaş küresel geçiş ve dönüşüm dinamiklerinin kamu politikası üretim süreçlerine etkisini analiz etmeyi amaçlamaktadır. Çalışmada, nitel araştırma yöntemi kullanılmış; ilgili literatür taraması ile teorik bir temel oluşturulmuş ve dijitalleşme, çevre politikaları ve uluslararası ilişkiler bağlamında örnek olay analizlerine yer verilmiştir. Kingdon’ın teorisine göre politika değişimi; sorun akışı, politika akışı ve siyaset akışı olmak üzere üç bağımsız sürecin belirli bir zaman aralığında kesişmesiyle oluşan “politika pencereleri” aracılığıyla mümkün hale gelmektedir. Bulgular, dijital dönüşümde kamu hizmetlerinde yaşanan bürokratik verimsizliklerin sorun akışını, e-devlet ve yapay zekâ çözümlerinin ise politika akışını temsil ettiğini; yeşil dönüşümde iklim krizi, çevresel bozulma ve kaynak kıtlığı gibi unsurların sorun akışını, yenilenebilir enerji politikalarının ise çözüm alternatiflerini yansıttığını ortaya koymaktadır. Aynı şekilde, çok kutuplu jeopolitik düzende savaşlar, enerji krizleri ve göç dalgalarının sorun akışını; çok taraflı diplomasi ve bölgesel iş birliklerinin ise politika akışını oluşturduğu görülmüştür. Bu bağlamda, politika girişimcilerinin stratejik müdahaleleri ve siyasal fırsat yapısının uygunluğu, politika pencerelerinin açılması ve politika değişiminin gerçekleşmesinde belirleyici rol oynamaktadır. Sonuç olarak, Çoklu Akışlar Teorisi, kamu politikası süreçlerinin doğrusal olmayan, karmaşık ve belirsiz doğasını anlamada etkili bir analitik çerçeve sunmakta; aktörlerin rolünü, zamanlamayı ve geçici fırsatları vurgulayarak başarılı dönüşüm stratejilerinin geliştirilmesine katkı sağlamaktadır.

This work presents an efficient method for mapping the electromagnetic characteristics of an electric machine, with low errors, using multiple neural networks and physical dependencies. To estimate the impact of design changes on production, an analysis of interdependencies between product parameters and production processes was conducted. The surrogate models allow a fast computation of the adapted machine speed torque characteristics and derived targets like corner point or drive cycle efficiency. In combination with the developed material cost function and the production influence function a paretooptimization is carried out. This work demonstrates how changes in target values affect material costs and the necessary production adjustments, using the position of the corner point and different efficiency levels as an example. The presented approach offers the opportunity to adapt existing machine designs towards a wide range of changed requirements, which lowers development costs and increases the utilization of existing production facilities for small quantities.

BACKGROUND:Timely identification of mild cognitive impairment (MCI) is critical for maximizing early intervention opportunities in older adults at risk for dementia. This study evaluated the feasibility, acceptability, and validity of novel digital cognitive tests in primary care.METHODS:In a two-phase pilot study across three clinics, 51 older adults completed digital cognitive assessments remotely on personal devices followed by supervised tablet-based cognitive screening in-clinic and the Montreal Cognitive Assessment (MoCA). Surveys and interviews assessed patient and provider acceptability. Digital test completion rates were examined to assess feasibility.RESULTS:Completion rates ranged from 61.5% - 76% for the at-home assessments and 81.8% for in-clinic testing. Participants generally preferred at-home testing. Providers found in-clinic testing acceptable but identified barriers related to device access and EMR integration. All but one digital test showed moderate correlations with the MoCA.CONCLUSION:Digital cognitive screening—whether remote or in-clinic—shows promise for primary care implementation.

A comprehensive overview is provided on factors and processes influencing the final quality of a cup of coffee, with an emphasis on the brewing method’s central role. Coffee quality assessment, both at the bean and cup level, combines objective parameters (color, moisture, bean defects, density) with a notable degree of subjectivity, as consumer sensory perception is ultimately decisive. The brewing technique is described as a critical determinant of the final chemical, physical, and sensory attributes. Key parameters such as aroma profile, pH, titratable acidity, total and filtered solids, lipid and fatty acid content, viscosity, foam (crema), and colorimetric indices are detailed as essential metrics in coffee quality evaluation. Roasting creates most of coffee’s key aroma compounds. The brewing method further shapes the extraction of both volatile and other bioactive compounds like caffeine, chlorogenic acids, and lipids. Brewing methods significantly affect acidity, “body,” and crema stability, while water quality, temperature, and pressure are shown to impact extraction results and sensory properties. Attention is paid to how methods such as Espresso, filter, French press, and cold brew yield distinct physicochemical and sensory profiles in the cup. Overall, the review highlights the multifaceted nature of coffee cup quality and the interplay between raw material, processing, and preparation, ultimately shaping the coffee sensory experience and market value.

BackgroundCystoisospora suis (C. suis) infects piglets in their first week of life and can subsequently lead to diarrhoea and production losses. The detection of C. suis oocysts relies mostly on the collection of piglet faeces as sampling material and analysis through flotation and autofluorescence microscopy, which involves repeated sampling. The objective of the present study was to evaluate the use of sponges for environmental sampling for the detection of C. suis via real-time PCR and its suitability for surveillance programs applied on farms.ResultsAll farms included in the study were positive for C. suis according to qPCR, with positivity rates ranging from 20 to 100%. The frequency of positive cases was 68% for faecal samples and 67% for samples collected by sponges. The alignment between the different sampling protocols was 100% achieved at the farm level. In the case of the individual pair samples, a difference in 27 samples was observed (10.8%). Considering the faecal sampling strategy as the gold standard, the sensitivity of the sampling protocol with sponges was 91.2%, and the specificity was 84.8%. Compared with the sponge-collected samples, the faecal samples presented slightly greater DNA masses, with a correlation coefficient of r = 0.51, indicating a moderate positive relationship between the two sampling methods. An influence towards a higher DNA load with samples with a pasty and semiliquid consistency was observed, mainly in the case of the sponge technique.ConclusionsOur results indicate that the collection of faecal samples at the litter or farm level and comparisons with environmental samples yield similar detection rates when sampling is combined with qPCR. From that perspective, the use of sponges for the detection of C. suis in organic material from the farrowing crate environment can be considered a good alternative to the more laborious and time-consuming collection of faecal samples.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40813-025-00454-5.

Lower Silesia was and is a borderland region, a meeting place of old and bordering cultures, an interpenetration of patterns, behaviors, customs, economic and family connections. Its cultural heritage included the culture of the entire immigrant population, its products and traditions, and the so-called monuments of the past. The process of growing into a regional reality was paradoxically hampered by the policy of national homogenization, which left no room for regional differences. In a period of intense globalization, the question of the possibility of preserving this original culture arises. What is needed is the transmission of cultural heritage, history, living tradition, not a relic, created today. The basis is the transmission and acceptance by subsequent generations of inherent values.

Zinc tin oxide (ZTO) is investigated as a photoluminescent sensor for oxygen (O2); chemisorbed oxygen quenches the luminescence intensity. At the same time, ZTO is also studied as a resistive sensor; being an n-type semiconductor, its electrical conductance decreases by adsorption of oxygen. Both phenomena can be exploited for quantitative O2 sensing. The respective sensor responses can be described by the same modified Stern-Volmer model that distinguishes between accessible and non-accessible luminescence centers or charge carriers, respectively. The impact of the temperature is studied in the range from room temperature up to 150 °C.

Tabletop simulation can be used to support and test system processes for clinical workflows. This paper will describe an innovative approach to testing change in clinical workflows for direct admissions to the operating room and interventional radiology departments in a 700-bed urban hospital in the Pacific Northwest and will highlight the specific benefits to nurse leaders. The simulation exercise involved key stakeholders and subject matter experts from various departments and aimed to evaluate the process workflow, provoke discussion on gaps, uncover improvement opportunities, and formulate recommendations. The simulation experience was broadly acknowledged by those involved as novel, engaging, suitable for complex process changes in health care settings and promoting valuable collaboration.