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إنه هو. لا أستطيع، بالركون إلى خفقات قلبي، أن أخدع نفسي. أعرف أنه من المتعذر تصديق هذا الذي أقول ؛ هذا اليقين المفاجئ، فليكن. نهضت، تاركة كأسي الملآن على الطاولة، وسددت حسابي ولحقت به. كان يمشي بسرعة، كما أمشي أنا. راقني اختياره ملبسه، وضيق وركيه، وجمال منكبيه. لا أريد أن أضيعه. على بعد شارع أو شارعين من هنا، ولج رواق مبنى واختفى. حينما وصلت ودفعت، من ثم، الباب الثقيل، كان هو قد دخل إلى إحدى الشقق، ولكن أية شقة يا ترى؟ ليس ثمة صوت في بئر السلم، ولا يزال المصعد في الطابق الأرضي ساكنا، كيف لي أن أعرف؟ صعدت بهدوء ومن دون ضجة. ثمة بساط يغطي الدرجات. إنه مبنى برجوازي ذو ثلاثة طوابق، وفي كل قرص من أقراص الدرج بابان، وعلى معظم الأبواب توجد لوحة نحاسية. كان الصمت يخيم على بعض الشقق، وتصدر من بعضها الآخر أصوات وضجيج أو رنين هاتف. لم ألبث أن نزلت، ومخافة أن أمسك متلبسة بغتة وأنا أقف هكذا بلا حراك، أنظر وأعاين وأتنصت.

Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). The 2023–24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6–24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016–17, 2017–18, 2018–19, 2019–20, and 2022–23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023–24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the catch-up group and 3188 (95·4%) of 3340 in the seasonal group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6–90·2). Effectiveness was 86·9% (69·1–94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9–78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0–73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5–90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24–32). No severe adverse events related to nirsevimab were registered. Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. Sanofi and AstraZeneca. For the Spanish translation of the abstract see Supplementary Materials section.

هناك كلمات تسمو بمن ينطقها كما تسمو بسامعيها فوق أنفسهم. هناك خطابات غيرت مجرى الأحداث، ومصير بلد بأكمله، وتاريخ العالم، وغيرت حتى نفوسا بشرية يموت الرجال وتمحي آثارهم ولكن كلماتهم تحيا وتضيء قبورهم كما تضيء شعلة خالدة. أولئك الذين تم إسكاتهم هم الذين يحدثوننا بصوت أعلى.\"هذا ما يقوله دومينيك جامي أسروا انتباه الجموع المحتشدة وغيروا مجرى التاريخ، ربما : من جان جوريس انتهاء بالدالاي لاما الرابع عشر، لجأ العظماء إلى سحر البيان في سبيل توعية الضمائر وتحفيز الخيال والاستفادة من الالتزام. بعد أربعين سنة من اغتيال مارتن لوثر كينغ يقوم دومينيك جاميه وهو كاتب وصحفي ومدير سابق لمكتبة فرنسا الوطنية، يقوم بتقديم عشرين خطابا أثرت في القرن العشرين ويعلق عليها. عشرون قطعة من الفصاحة تحمل تواقيع جوريس، ويلسون، غاندي، روزفلت، تشرشل، ديغول، كينيدي، لوثر كينغ، تشي غيفارا، الليندي، بادينتر، ميتيران، جان بول الثاني، عرفات، مانديلا، شيراك، أو أيضا تنزان غياستو وهو الدالاي لاما الحالي.

The detection of metastases in patients with a diagnosis of uveal melanoma (UM) is a controversial issue. While only 1% of the patients have detectable metastases at the time of diagnosis, up to 30% of them will develop liver metastases within 5 years of treatment. UM spreads hematogenously, therefore, blood biomarkers may be helpful for prognosis and monitoring the disease progression. Despite the great progress achieved thanks to the genetic analysis of UM biopsies, this is an invasive technique and is limited by the heterogeneity of the tumor. The present review considers the current understanding in the field regarding biomarkers for the diagnosis and prognosis of UM and its metastasis, primarily to the liver. General covered topics include non-conventional markers such as proteins previously identified in cutaneous melanoma and UM cell lines, circulating tumor cells, microRNAs (miRNA), and circulating DNA, and how each may be critical in the development of novel blood biomarkers for UM.

There are increasing efforts to engineer functional compartments that mimic cellular behaviours from the bottom-up. One behaviour that is receiving particular attention is motility, due to its biotechnological potential and ubiquity in living systems. Many existing platforms make use of the Marangoni effect to achieve motion in water/oil (w/o) droplet systems. However, most of these systems are unsuitable for biological applications due to biocompatibility issues caused by the presence of oil phases. Here we report a biocompatible all aqueous (w/w) PEG/dextran Pickering-like emulsion system consisting of liposome-stabilised cell-sized droplets, where the stability can be easily tuned by adjusting liposome composition and concentration. We demonstrate that the compartments are capable of negative chemotaxis: these droplets can respond to a PEG/dextran polymer gradient through directional motion down to the gradient. The biocompatibility, motility and partitioning abilities of this droplet system offers new directions to pursue research in motion-related biological processes. Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.

Polydimethylsiloxane (PDMS) is a dominant material in the fabrication of microfluidic devices to generate water-in-oil droplets, particularly lipid-stabilized droplets, because of its highly hydrophobic nature. However, its key property of hydrophobicity has hindered its use in the microfluidic generation of oil-in-water droplets, which requires channels to have hydrophilic surface properties. In this article, we developed, optimized, and characterized a method to produce PDMS with a hydrophilic surface via the deposition of polyvinyl alcohol following plasma treatment and demonstrated its suitability for droplet generation. The proposed method is simple, quick, effective, and low cost and is versatile with respect to surfactants, with droplets being successfully generated using both anionic surfactants and more biologically relevant phospholipids. This method also allows the device to be selectively patterned with both hydrophilic and hydrophobic regions, leading to the generation of double emulsions and inverted double emulsions. Microfluidics: Patterned channels pave way for new applications A simple, low-cost and versatile technique for making reusable microfluidic devices with patterned channels promises new applications. Microfluidic chips have found use in technologies as diverse as fuel cells and the construction of artificial cell models and organs-on-chip. However, the hydrophobic nature of polydimethylsiloxane (PDMS), which is commonly used in chip fabrication, limits potential applications. This spurred Tatiana Trantidou and her colleagues at Imperial College London and University College London, in the United Kingdom, to make PDMS with a hydrophilic surface by coating microfluidic channels with polyvinyl alcohol immediately after plasma treatment. Their innovative technique enables selective patterning of the channels with defined wettability characteristics, facilitating the production of emulsions, double emulsions and inverse double emulsions. The work could expand the use of microfluidic devices to various applications in pharmaceuticals, food science and synthetic biology.

In the discipline of bottom-up synthetic biology, vesicles define the boundaries of artificial cells and are increasingly being used as biochemical microreactors operating in physiological environments. As the field matures, there is a need to compartmentalize processes in different spatial localities within vesicles, and for these processes to interact with one another. Here we address this by designing and constructing multi-compartment vesicles within which an engineered multi-step enzymatic pathway is carried out. The individual steps are isolated in distinct compartments, and their products traverse into adjacent compartments with the aid of transmembrane protein pores, initiating subsequent steps. Thus, an engineered signalling cascade is recreated in an artificial cellular system. Importantly, by allowing different steps of a chemical pathway to be separated in space, this platform bridges the gap between table-top chemistry and chemistry that is performed within vesicles. In biological systems, cells are divided into compartments, typically with lipid layers. Here, the authors design a multipart vesicle system for sequential enzymatic reactions, where the product from one reaction traverses into the next, allowing multiple spatially separated reaction steps.

Constructing higher-order vesicle assemblies has discipline-spanning potential from responsive soft-matter materials to artificial cell networks in synthetic biology. This potential is ultimately derived from the ability to compartmentalise and order chemical species in space. To unlock such applications, spatial organisation of vesicles in relation to one another must be controlled, and techniques to deliver cargo to compartments developed. Herein, we use optical tweezers to assemble, reconfigure and dismantle networks of cell-sized vesicles that, in different experimental scenarios, we engineer to exhibit several interesting properties. Vesicles are connected through double-bilayer junctions formed via electrostatically controlled adhesion. Chemically distinct vesicles are linked across length scales, from several nanometres to hundreds of micrometres, by axon-like tethers. In the former regime, patterning membranes with proteins and nanoparticles facilitates material exchange between compartments and enables laser-triggered vesicle merging. This allows us to mix and dilute content, and to initiate protein expression by delivering biomolecular reaction components. Assembly of higher-order artificial vesicles can unlock new applications. Here, the authors use optical tweezers to construct user-defined 2D and 3D architectures of chemically distinct vesicles and demonstrate inter-vesicle communication and light-enabled compartment merging.

Cell-sized vesicles have tremendous potential both as miniaturised pL reaction vessels and in bottom-up synthetic biology as chassis for artificial cells. In both these areas the introduction of light-responsive modules affords increased functionality, for example, to initiate enzymatic reactions in the vesicle interior with spatiotemporal control. Here we report a system composed of nested vesicles where the inner compartments act as phototransducers, responding to ultraviolet irradiation through diacetylene polymerisation-induced pore formation to initiate enzymatic reactions. The controlled release and hydrolysis of a fluorogenic β-galactosidase substrate in the external compartment is demonstrated, where the rate of reaction can be modulated by varying ultraviolet exposure time. Such cell-like nested microreactor structures could be utilised in fields from biocatalysis through to drug delivery. Matryoshka doll-like, nested vesicles, each containing a different ingredient to a chemical reaction, can serve as microreactors. Here, the authors developed a system in which mixing of the ingredients can be induced by irradiation with ultraviolet light.

To date, reconstitution of one of the fundamental methods of cell communication, the signaling pathway, has been unaddressed in the bottom-up construction of artificial cells (ACs). Such developments are needed to increase the functionality and biomimicry of ACs, accelerating their translation and application in biotechnology. Here, we report the construction of a de novo synthetic signaling pathway in microscale nested vesicles. Vesicle-cell models respond to external calcium signals through activation of an intracellular interaction between phospholipase A2 and a mechanosensitive channel present in the internal membranes, triggering content mixing between compartments and controlling cell fluorescence. Emulsion-based approaches to AC construction are therefore shown to be ideal for the quick design and testing of new signaling networks and can readily include synthetic molecules difficult to introduce to biological cells. This work represents a foundation for the engineering of multicompartment-spanning designer pathways that can be utilized to control downstream events inside an AC, leading to the assembly of micromachines capable of sensing and responding to changes in their local environment.