Large language models (LLMs) can generate persuasive narratives that shift agent behavior in multi-agent systems, but deploying raw, unstructured text as an influence mechanism offers no formal guarantees on effectiveness, interpretability, or controllability. We introduce the LLM Influence Compiler (LIC), a solver-critic pipeline that compiles natural-language cooperation directives into structured, parameterized influence policies defined over a five-field schema: network targeting, narrative theme, intensity, deployment timing, and compiler confidence. Each compiled policy is diffused through a network of numerical agents via an exposure model incorporating fatigue decay, susceptibility heterogeneity, and backlash. Evaluation spans nine controlled experiment blocks comprising more than 200 simulation runs across four topologies (Barabási-Albert, small-world, Erdős-Rényi, modular SBM), four network sizes (n ∈ {80, 160, 320, 640}), five LLM backbones, and two non-stationary perturbations. Compiled policies raise the mean cooperation rate to 0.826 ± 0.010 (95% bootstrap CI [0.819, 0.834]), an 8.6% relative improvement over the unstructured baseline (0.760 ± 0.005, Mann-Whitney p Bonf = 0.040, Cohen's d = 7.90). A controlled decomposition attributes the gain to network-aware targeting (ca. +4.5 pp), dose calibration (+1.9 pp), and an intervention floor (+1.5 pp); the residual contribution of full LLM compilation over a hand-coded rule with the same parameters is statistically indistinguishable from zero under stationary conditions. Under structural non-stationarity (mid-simulation graph rewire), the LLM-mediated re-deployment architecture significantly outperforms a frozen rule (paired t-test p < 0.001, paired Cohen's d = 2.27, 8/8 seeds). Adversarial stress testing confirms that the critic correctly flags 20/20 risky policies as high risk and rejects them, while passing a moderate-baseline policy at medium risk in all 5/5 trials. The compiler abstraction converts an opaque generative process into a decomposable, auditable policy object whose components can be independently attributed, compared, and governed, laying the groundwork for constitutional oversight of LLM-mediated influence in artificial societies.
Controlling protein unfolding and translocation through solid-state nanopores remains a significant challenge due to the steep entropic barriers and the propensity for kinetic jamming. We propose a stepped graphene nanopore architecture designed to decouple the thermodynamic and kinetic requirements of the translocation process. Using all-atom molecular dynamics simulations, we demonstrate that the stepped geometry reconfigures the electrostatic potential, smoothing the field gradient and partitioning the entropic barrier into manageable stages. Our results reveal a non-monotonic dependence of translocation success on the average trans-pore electric field, identifying an intermediate-field kinetic regime around 0.048 V Å-1 in which electrophoretic driving and protein conformational relaxation are better balanced under the present accelerated-sampling conditions. At a lower field of 0.024 V Å-1, translocation is suppressed by entropic rejection as the driving force fails to overcome the entry barrier. Conversely, at an elevated field of 0.096 V Å-1, a critical rate mismatch occurs: the excessive drift velocity outpaces the unfolding rate, triggering lateral buckling and irreversible steric jamming at the final constriction. Compared with a conventional single-step nanopore, the stepped architecture facilitates high-fidelity observation of unfolding intermediate states at moderate driving forces, thereby avoiding excessive driving conditions that promote kinetic jamming and reduce structural resolution. By establishing a kinetic-competition framework based on native-contact loss, residue-passage timing, and productive axial linearization, this study provides a physical framework for designing blockage-resistant nanopore sensors for high-resolution protein structural analysis.
Although obesity is increasingly recognized as a chronic, relapsing disease, clinical consultations remain inconsistently delivered, often perceived by patients as generic, stigmatizing, and insufficiently person-centered. While dissatisfaction with weight-related care is well documented, limited research has systematically examined how patients themselves define the core features of an effective obesity consultation. This study aimed to develop a patient-informed framework for clinical obesity consultations by exploring the expectations and experiences of individuals with lived experience of obesity. A qualitative descriptive design was employed. Twenty adults (BMI ≥ 27 kg/m2 with at least one obesity-related complication) who had received treatment for obesity were recruited via purposive sampling. Semi-structured interviews were conducted via Zoom, transcribed, anonymized, and analyzed using reflexive thematic analysis. Coding was inductive and organized using MAXQDA. Participants articulated a coherent and detailed model of the ideal clinical encounter, extending beyond previously reported dissatisfaction. Five key themes were identified: (1) the need for consent-based and context-sensitive initiation of weight discussions; (2) the rejection of moralizing or reductive language in favor of medically grounded and neutral communication; (3) recognition of obesity as heterogeneous, multifactorial disease requiring individualized assessment; (4) expectations for clear, evidence-based information on treatment options and likely outcomes; and (5) a strong preference for ongoing, relationship-based support rather than episodic advice. Patients revealed that unmet informational and relational needs, especially regarding clinical competence, emotional sensitivity, and collaborative treatment planning, were primary barriers to trust and engagement. This study advances current understanding by proposing a patient-defined model for obesity consultations, with implications for improving clinical communication, shared decision-making, and continuity of care.
Membrane-based processes offer promising sustainable alternatives for the decolourisation and purification of starch hydrolysates, yet membrane selection and operating conditions remain the most critical challenges. This study systematically evaluates the performance of polymeric ultrafiltration (UF) and nanofiltration (NF) membranes for starch hydrolysate syrup treatment. Experiments were conducted in a lab-scale cross-flow filtration system using five UF and three NF flat-sheet polymeric membranes under varying temperatures, transmembrane pressures, and feed concentrations. Separation performance was assessed through colour removal, sugar recovery, permeate flux, and alongside indicators of fouling behaviour. UF membranes with molecular weight cut-offs of 100, 70, and 5 kDa exhibited the most favourable performance at 60 °C and 8 bar, achieving partial colour removal (18-32%) with high permeate fluxes (84-130 kg·m-2·h-1) and limited sugar losses (0.7-19.9%). NF membranes showed significantly higher colour rejection (32-100%) but were associated with substantial sugar losses (up to 96%), limiting their applicability for selective decolourisation; however, their high sugar retention capacity suggests potential for product concentration and the removal of low-molecular-weight impurities. Overall, UF represents a suitable approach for partial colour removal in starch hydrolysates, while NF may be better suited for product concentration and the removal of low-molecular-weight impurities, as well as auxiliary applications such as water recovery. These findings provide a systematic basis for membrane selection and process optimisation in industrial starch hydrolysate purification.
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Anthralin has a long history as a topical treatment for psoriasis, where it reduces keratinocyte hyper-proliferation and effectively clears plaques. While it lowers inflammatory markers in psoriatic skin, it paradoxically induces inflammation in healthy skin through reactive oxygen species (ROS) and related pathways. However, its precise mechanism of action remains incompletely understood. Interestingly, the once undesirable pro-inflammatory effect in healthy skin may now represent a valuable adjuvant property for transcutaneous immunization (TCI). In particular, combining anthralin with the TLR7 agonist imiquimod (IMQ) elicits strong cytotoxic T-cell responses in pre-clinical studies. When paired with antigenic peptides that can penetrate the skin, this immunization approach is especially promising in the context of cancer therapy, given the central role of cytotoxic T-cells in tumor rejection. However, current evidence is largely derived from mouse models, but its efficacy and safety in humans remain to be established. This review therefore examines whether anthralin can be repurposed as a cutaneous adjuvant for transcutaneous immunization, and which mechanistic and translational constraints must be overcome before human application.
Rejection remains a major barrier to long-term kidney allograft survival, and pre-transplant risk stratification remains incomplete. This study evaluated whether pre-transplant serum Fourier-transform infrared (FTIR) spectra, analyzed using machine learning methods, could identify kidney transplant recipients at increased risk of subsequent biopsy-proven rejection. In this retrospective single-center study, 80 pre-transplant serum samples collected on the day of transplantation were initially evaluated; after spectral quality control, 79 samples were retained for analysis. FTIR spectra were acquired in transmission mode and analyzed in the 600-1900 cm-1 and 2800-3400 cm-1 regions. Multiple preprocessing strategies were assessed, including Rubber Band baseline correction, vector normalization, and first- and second-derivative transformation, with and without normalization. Naïve Bayes classifiers with Leave-One-Out Cross-Validation and Fast Correlation-Based Filter feature selection were applied. Exploratory analysis showed broad overlap between groups, indicating a subtle multivariate spectral signal. In the initial exploratory workflow, classifier performance depended strongly on preprocessing and feature selection. Because non-nested feature selection may produce optimistic estimates, the main supervised analysis was repeated using FCBF nested within each LOOCV training fold. The best-performing nested model was obtained using second derivative transformation followed by normalization in the combined 600-1900 and 2800-3400 cm-1 regions, achieving an AUC of 0.837, accuracy of 0.747, sensitivity of 0.675, specificity of 0.821, balanced accuracy of 0.748, and F1-score of 0.730. Permutation testing with 1000 label-randomized repetitions supported performance above chance expectation, with no permuted model reaching the observed AUC (empirical p = 0.000999). Pre-transplant serum FTIR spectroscopy combined with leakage-aware nested machine learning analysis identified an internally validated spectral signal associated with subsequent biopsy-proven rejection. These findings support FTIR as a promising complementary and hypothesis-generating approach for pre-transplant biochemical risk phenotyping, requiring external multicenter validation before clinical application.
Nanofiltration (NF) membranes have emerged as promising candidates for use in low-salt-rejection reverse osmosis (LSRRO) for high-salinity brine concentration, yet their performance under high operating pressures remains poorly understood. Here, we systematically evaluate the feasibility of NF membranes for LSRRO under elevated pressures using a commercial state-of-the-art membrane. Experimental results and structural characterization show that, while the selective active layer remains structurally and functionally stable, the porous support layer undergoes severe compaction, leading to a pronounced decline in water permeance. To elucidate this behavior, we develop a framework that integrates polymer-network thermodynamics, finite-deformation kinematics, and porous-media transport. The framework quantitatively predicts the pressure-dependent permeance of the membrane and clarifies transport limitations under high-pressure operation. Sensitivity analysis further reveals that membrane performance at high pressures is governed primarily by the mechanical robustness of the support layer, rather than its initial porosity or hydrophilicity. Our results indicate that membrane design for LSRRO should prioritize resistance to compaction. Overall, this study establishes a predictive and mechanistically informed framework for evaluating and designing NF membranes for minimal or zero liquid discharge (MLD/ZLD) applications.
This study presents a systematic comparison of commercial reverse osmosis (RO) and nanofiltration (NF) membranes for the separation of inorganic and organic carbonates from aqueous solutions, providing insight into the roles of membrane pore structure and surface charge in governing separation mechanisms. Membrane molecular weight cut-off (MWCO), zeta potential, and thermal stability were characterized and correlated with separation performance. The RO membrane exhibited a lower MWCO and a more negative surface charge than the NF membrane, resulting in superior rejection of both inorganic and organic carbonates. For inorganic carbonates, rejection increased with pH owing to enhanced carbonate ionization and stronger electrostatic repulsion, reaching 91-98% for the RO membrane compared with 60-95% for the NF membrane. In contrast, the rejection of neutral organic carbonates was governed primarily by steric exclusion, with the RO membrane achieving approximately 80% rejection, whereas the NF membrane exhibited negligible removal. These findings demonstrate the combined influence of membrane pore size and surface charge on carbonate separation and provide practical guidance for selecting commercial membranes for efficient carbonate removal in water treatment applications.
Antibody-mediated rejection (AMR) remains a leading cause of kidney allograft failure, with both HLA and non-HLA antibodies implicated in its pathogenesis. The contribution of non-HLA antibodies (non-HLA Abs) to microvascular inflammation (MVI) and graft outcome, particularly in cases lacking donor-specific anti-HLA antibodies (HLA-DSAs), remains incompletely understood. We analyzed 571 post-transplant serum samples from 326 patients with histological features of AMR (AMRh) and 164 stable control individuals. Non-HLA Abs were detected using the previously developed Non-HLA Antibody Detection Immunoassay (NHADIA), and associations were examined with histological lesions, AMRh persistence, and graft outcomes. Biopsies were scored according to Banff 2022 criteria, and patients were stratified by HLA-DSA and NHADIA status. External validation was also performed in an independent kidney transplant cohort that included 211 biopsies from 189 patients. NHADIA values were significantly higher in patients with AMRh compared to controls, regardless of HLA-DSA status. NHADIA values correlated with the severity of glomerulitis, peritubular capillaritis and global MVI scores. In patients with AMRh and HLA-DSAs, non-HLA Abs remained independently associated with MVI severity. Follow-up biopsies revealed persistent AMR lesions in patients with both HLA-DSAs and non-HLA Abs. Allograft survival was lowest in double-positive patients, and NHADIA positivity independently and significantly predicted graft loss (hazard ratio2.25, 95% confidence interval 1.03-4.92). Association of non-HLA Abs with Banff lesions severity and death-censored graft survival was replicated in the external validation cohort. Post-transplant detection of non-HLA antibodies identifies a distinct subset of AMR with more severe histology and worse graft prognosis, particularly when coexisting with HLA-DSAs. Integrating non-HLA Ab testing into current diagnostic frameworks may refine AMR classification and improve risk stratification.
Non-operative management (NOM) of acute appendicitis has been validated by trials such as Appendicitis Acuta and Comparison of Outcomes of Antibiotic Drugs and Appendectomy, with treatment failure rates of approximately 25-30% within one year, raising hopes that a less invasive approach could become the standard of care. However, the conditions underpinning these trials, such as early presentation, reliable imaging, uninterrupted access to antibiotics, structured follow-up, and immediate surgical backup, are not consistently available in Honduras. Up to 54% of patients at a Honduran tertiary centre present with gangrenous or perforated disease, considerably reducing the proportion of patients eligible for NOM, while sociocultural practices such as abdominal manipulation (sobada), weak referral networks, and limited diagnostic capacity further delay access to care. We argue that NOM cannot currently be recommended as a standard approach across the Honduran health system, although it may have a role in well-resourced tertiary centres. Importantly, this is not a rejection of NOM evidence: the primary drivers of poor outcomes in Honduras, late presentation and limited system capacity, are not addressed by NOM and could worsen if applied without adequate infrastructure. We propose that strengthening point-of-care diagnostics, referral pathways, antibiotic supply chains, and follow-up capacity should be the immediate priority, both to improve outcomes directly and to build the foundations for selective NOM implementation as the health system evolves.
This study assessed community awareness, knowledge, and attitudes toward genetic disorders associated with consanguineous marriage and evaluated acceptance of premarital/genetic screening among adults in Al-Baha, Saudi Arabia. A descriptive cross-sectional study was conducted in late 2025 (October-November) among adults (≥18 years) residing in Al-Baha using a structured, self-administered electronic questionnaire distributed through social media, university channels, and community networks. A total of 673 complete responses were analysed (mean age 32.67 ± 13.12 years; 50.4% female; 49.8% married). Consanguinity was common (tribal endogamy 42.5%; extended-family endogamy 40.0%), with 20.5% reporting first-cousin and 12.9% second-cousin marriage; parental and grandparental consanguinity were reported by 70.7% and 70.6%, respectively. Familial genetic/health burden was notable, particularly hereditary visual impairment (34.8%), thalassemia/hereditary anemia (25.7%), and hearing impairment/delayed speech (20.5%). Knowledge was generally good (84.4% recognized increased autosomal recessive risk; 89.3% endorsed genetic counselling benefits), but gaps persisted (33.1% did not know premarital screening includes SCD/thalassemia; only 42.1% correctly rejected the absence of a sensory-disorder link). Attitudes strongly supported prevention (premarital screening mandatory 93.9%), although within-family/tribe marriage remained widely endorsed (80.4%). Higher knowledge was associated with more favourable attitudes (OR = 2.25, p < 0.001); consanguinity with higher familial burden (OR = 2.45, p < 0.001); and familial burden with higher knowledge (OR = 1.65, p = 0.003) and more favourable attitudes (OR = 1.84, p < 0.001). A discordant profile of high preventive attitudes coexisting with acceptance of within-family or tribal marriage was observed in 51.9% of participants. Adults in Al-Baha demonstrated strong acceptance of preventive genetic services alongside generally good knowledge; however, persisting gaps, particularly related to awareness of specific service components and recognition of sensory-disorder links, support targeted community education and strengthened genetic counselling to optimize informed marital and reproductive decision-making.
Patient and public involvement (PPI) improves patient-targeted guideline material and is recognised internationally as essential in guideline development. Whilst current research has focussed on PPI both in guideline development and palliative care, evidence regarding its implementation in developing patient-targeted guideline material is limited. To explore participants' experiences and identify supportive and challenging factors in the participatory development of patient-targeted guideline material in palliative care. Qualitative evaluation of the participatory development process (04/2024 - 09/2024) of a patient guide to a German best practise recommendation on intentional sedation using questionnaires with open-ended questions followed by semi-structured interviews. Data were analysed using structuring qualitative content analysis according to Kuckartz. Four PPI members and four healthcare professionals randomly selected from the editorial panel tasked with developing the patient guide. The participatory approach with experienced PPI-members as experts for lay-comprehensibility fostered an equal and respectful environment, allowing all participants to contribute. Despite successful organisation and communication, obstacles arose regarding time management and technical challenges with hybrid sessions and digital co-working formats. The participants did not require additional methodological training. Working in subgroups proved effective and offered emotional support but carried the risk of creating inequalities. PPI can be supported by recruiting experienced PPI advisory board members, providing flexibility through hybrid sessions and managing emotional distress through creating a save atmosphere with peer support in subgroup sessions. Communication barriers in hybrid meetings, rejection of digital co-working formats, inattention to PPI in subgroup sessions and time management issues must be considered when planning a project. Involving patients and the public (PPI) in creating patient guidelines makes these guidelines more focused on patients’ needs, more trustworthy, and easier to use. Therefore, PPI is recognised as important worldwide, but it is not yet clear how to do it in the best way. We wanted to find out how to best support PPI when creating patient guidelines in palliative care. In 2024, we created a patient guide on intentional sedation, a treatment option in palliative care. Our panel included patient and public representatives and healthcare specialists. After finalising the patient guideline, we asked eight participants about their experiences. Their feedback revealed several challenges and helpful factors for involving patients and the public: Challenges: - Communication can be difficult when meetings are both online and in-person. - Some participants do not like using digital tools at home to comment on texts. - During panel meetings, discussions take up a lot of time. Some participants even wished for more time to talk. - In small group discussions, patient representatives sometimes felt overshadowed by healthcare specialists. Helpful factors: - It helps to choose a small group of patient representatives who have experience with research projects. More members of the public can join in by giving feedback on the final draft. - Having meetings both online and in-person gives flexibility to carers and people with limited mobility. - Splitting a large panel into smaller groups helps people to join in and to provide emotional support. - The co-creation between patient representatives and health professionals is sufficient to create a patient guideline in plain language; no resources need to be spent on training in medical language. We hope these challenges and helpful factors will improve the involvement of patients and the public in creating patient guidelines. We also hope that more guidelines will be developed with PPI in the future.
Solid organ transplantation is the optimal treatment for patients living with end-stage organ failure. Globally, the majority of organ donors are deceased, most commonly following brainstem death. The process of brain death is known to cause significant injury to organs. Therefore, efforts to optimise the pre-donation care of these donors should be maximised to achieve improved recipient outcomes. To assess the benefits and harms of therapeutic donor hypothermia in recipients of organs donated from brain-dead donors. We searched Cochrane Kidney and Transplant's Specialised Register, CENTRAL, MEDLINE, Embase and two trials registers up to 03 September 2025. All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) investigating therapeutic donor hypothermia compared with donor normothermia following brainstem death to improve the quality of transplanted organs. Critical outcomes were post-transplant outcomes (delayed graft function (DGF), graft survival), utilisation and donor adverse events. Important outcomes were patient survival, primary nonfunction, acute rejection, quality of life and cardiovascular disease. We used Cochrane's risk of bias 1 tool. Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted data. We used random-effects models for the meta-analysis. We assessed the certainty of evidence using the GRADE approach. We included four studies, enrolling 2096 donors. Two studies compared donor hypothermia versus normothermia in kidney transplantation. Two studies investigated kidney, heart, lung, liver and pancreas transplantations. Four studies assessed the impact of donor hypothermia compared with normothermia on kidney outcomes. Donor hypothermia may not reduce the rate of kidney DGF compared to donor normothermia (RR 0.87, 95% CI 0.71 to 1.08; I² = 57%; 4 studies, 3015 participants; low-certainty evidence). Donor hypothermia may not be associated with one-year kidney graft survival (HR 0.77, 95% CI 0.51 to 1.14; I² = 0%; 3 studies, 2075 participants; low-certainty evidence) or one-year patient survival in kidney transplant recipients (HR 0.81, 95% CI 0.42 to 1.57; 1 study, 526 participants; low-certainty evidence). No studies assessed the impact on primary non-function of the kidney or acute rejection. Evidence from only one RCT was available for other solid organ post-transplant outcomes. Donor hypothermia may show no difference to graft survival (lung transplant: HR 0.73, 95% CI 0.21 to 2.51; 1 study; low-certainty evidence; liver transplant: HR 0.85, 95% CI 0.35 to 2.06; 1 study; low-certainty evidence). Donor hypothermia has no impact on liver utilisation (RR 1.02, 95% CI 0.96 to 1.08; I² = 0%; 2 studies, 1259 participants; high-certainty evidence) and probably has no impact on the utilisation of the following organs: kidney (RR 0.99, 95% CI 0.95 to 1.03; I² = 44%; 4 studies, 4265 participants; moderate-certainty evidence); heart (RR 1.03, 95% CI 0.87 to 1.21; I² = 0%; 2 studies, 1259 participants; moderate-certainty evidence); lung (RR 0.97, 95% CI 0.85 to 1.11; I² = 0%; 2 studies, 2518 participants; moderate-certainty evidence); pancreas (RR 1.09, 95% CI 0.74 to 1.61; I² = 0%; 2 studies, 1259 participants; moderate-certainty evidence). Donor hypothermia may not affect the occurrence of donor adverse events (RR 1.28, 95% CI 0.45 to 3.62; I² = 12%; 3 studies, 2015 participants; low-certainty evidence). No data were available for primary nonfunction, acute rejection, quality of life or cardiovascular diseases. Most studies focused on kidney transplant outcomes, with limited data on other organs. The certainty of the evidence was generally low to moderate, primarily due to imprecision, high risk of reporting bias, or both. This review provides low-certainty evidence that donor hypothermia may have no impact on post-transplant outcomes. Donor hypothermia may not be associated with reduced organ utilisation. No safety concerns were identified, and donor hypothermia may not increase donor adverse events. No specific funding was received. Protocol (2023): doi:10.1002/14651858.CD015190.
Tacrolimus (TAC) is a cornerstone of immunosuppressive therapy after kidney transplantation but has a narrow therapeutic window, requiring strict therapeutic drug monitoring. Several analytical methods are available for serum concentration measurement and methodological interference may lead to clinically misleading results. We report the case of a 67-year-old female kidney transplant recipient who presented with persistently elevated tacrolimus concentrations despite drug discontinuation. TAC concentrations were initially measured using the affinity column-mediated immunoassay (ACMIA), showing markedly supratherapeutic values that prompted repeated suspension of the medication. Given the discrepancy between laboratory results and TAC withdrawal, measurement was repeated using the microparticle enzyme immunoassay (MEIA), which demonstrated undetectable results, confirming false-positive values associated with ACMIA interference. TAC was safely reintroduced at a reduced dose, with subsequent concentrations remaining within the therapeutic range. During follow-up, the patient developed antibody-mediated rejection, which was successfully treated and maintained good graft function. This case highlights the importance of recognizing analytical limitations of TAC assays and emphasizes that unexpected results should prompt confirmatory testing using alternative methodologies. Integration of clinical judgment with laboratory data is essential to avoid inappropriate immunosuppressive management and to ensure graft safety.
Early identification of rejection remains a critical unmet need in kidney transplantation, as conventional tools detect rejection only after irreversible allograft injury. The pre-transplant gut microbiome may provide novel predictive signals by modulating immune homeostasis. Pre-transplant stool samples underwent shotgun metagenomic sequencing. Composition, functional profiles, and networks were compared between rejection and non-rejection (protocol biopsy ≤ 2 weeks). A pre-specified SCFA biosynthetic KO panel was tested with FDR correction. Stepwise Random Forest models were developed with subgroup analyses and tested in a temporal validation cohort. Of 78 recipients, 26 (33.3%) developed biopsy-proven early acute rejection. Three taxa including Phascolarctobacterium faecium were FDR-significantly reduced. At the gene level, mcmB (a key propionate-biosynthetic enzyme) was the only KO reaching FDR significance in the pre-specified SCFA panel (q = 0.018). Network analysis revealed selective microstructural reorganization. AUC improved stepwise (0.565 → 0.681 → 0.765), was preserved across rejection subtypes (TCMR-spectrum 0.74; ABMR 0.85), and reached 0.721 in temporal validation with improved reclassification (NRI 0.11; IDI 0.055) and clinical net benefit at thresholds 0.2-0.5. Pre-transplant gut microbiome signatures were independently associated with early acute rejection. Microbiome-augmented models outperformed clinical-only models and remained robust in temporal validation, supporting microbiome-based pre-transplant risk stratification.
Glioblastomas, the most common and aggressive brain tumors in adults, present a significant therapeutic challenge. Despite the limited treatment options outlined by current guidelines, bevacizumab has emerged as a critical, yet controversial option. This study investigates the off-label use of bevacizumab in France, highlighting its therapeutic demand despite the absence of marketing authorization. Since the European Medicines Agency (EMA) rejected its application for glioblastoma treatment in 2009, it has not been re-evaluated at the European level. This research primarily aims to explore clinical practices surrounding bevacizumab's use and assess its relevance and potential benefits for patients with glioblastoma in real-world settings. A cross-sectional, observational epidemiological survey was conducted using data from ScanSanté® and feedback from hospitals in the Provence-Alpes-Côte d'Azur (PACA) and Corsica regions. These findings were then compared to literature data. In 2023, bevacizumab was used in 97.3% of hospital days related to malignant brain tumors treated off-label in France. Among off-label prescriptions for glioblastomas, 82.0% were for recurrent glioblastomas, 13.1% for newly diagnosed glioblastomas, and 4.9% had no precise diagnosis. Literature reviews indicate a favorable benefit-risk balance for certain patient profiles, particularly showing improved progression-free survival and quality of life when bevacizumab is employed. The significant off-label use of bevacizumab in glioblastoma treatment underscores an urgent therapeutic need in France. These findings were submitted to the French National Agency for the Safety of Medicines and Health Products (ANSM) to advocate for its regulated use in clinical practice.
Clinical pharmacists contribute pharmacotherapy expertise to antimicrobial stewardship (AMS), but antimicrobial prescribing remains a multidisciplinary process led by treating clinicians. In physician-centered hospital systems, pharmacists' contributions may be integrated into prescribing decisions to varying degrees depending on the organizational structures, interprofessional relationships, workflow integration, and prescribing cultures. This study aimed to explore how contextual and interprofessional factors shape the integration of clinical pharmacists' antimicrobial stewardship contributions within multidisciplinary prescribing decisions in Jordanian hospitals. A multi-site qualitative study was conducted across nine Jordanian hospitals. Semi-structured interviews were conducted with 26 clinical pharmacists involved in antimicrobial reviews in intensive care and general medical units. Interviews incorporated the critical incident technique to elicit examples of accepted and rejected stewardship recommendations. Data were analyzed using a realist-informed approach to develop context-mechanism-outcome configurations explaining variations in pharmacists' reported AMS contribution. Pharmacotherapy expertise was necessary but not sufficient for pharmacists' recommendations to shape antimicrobial prescribing. Leadership endorsement, structured multidisciplinary rounds, and formal documentation pathways activated mechanisms of legitimacy, credibility, and workflow visibility, supporting reported uptake of dose optimization, therapeutic drug monitoring, and selected de-escalation recommendations. In contrast, prescriber-led hierarchies, limited documentation pathways, workload pressures, and defensive prescribing cultures activated mechanisms of self-limitation, risk aversion, and limited recommendation uptake, particularly for discontinuation, duration control, and narrowing of broad-spectrum therapy. Strengthening AMS requires not only formal committees and guidelines but also team-based structures that integrate pharmacists' pharmacotherapy expertise into antimicrobial review while preserving clinicians' ultimate prescribing responsibility.
Sustainable water management demands efficient hypersaline treatment and salt recovery. Membrane distillation (MD) is promising but limited by the trade-off between permeability and wetting resistance in conventional hydrophobic membranes. Herein, we report a patterned covalent organic framework (COF) Janus membrane with a hydrophilic-hydrophobic architecture. This membrane is fabricated via trimesoyl chloride-triggered interfacial reassembly, enabling defect-free formation of a hydrophilic terephthaldehyde-piperazine COF layer with subnanometer pores on a hydrophobic polytetrafluoroethylene (PTFE) substrate. This structure leverages a synergistic "water enrichment-evaporation" mechanism, where confined pores and the patterned hydrophilic surface reorganize the hydrogen-bond network of water, dramatically accelerating transport and evaporation. The COF Janus membrane achieves >99.99% NaCl rejection and an ultrahigh water flux of 121.7 L m-2 h-1, a 72% improvement over the PTFE membrane. It also exhibits robust resistance to surfactant-induced wetting and oil fouling, ensuring long-term stability under harsh conditions. This work resolves the permeability-wetting trade-off in MD and establishes a versatile platform for next-generation high-performance desalination membranes.
Global freshwater scarcity and escalating hypersaline wastewater discharge challenge sustainable development. Solar-driven zero-liquid-discharge (SDZLD) technology addresses this by using localized solar heating to maximize freshwater recovery while minimizing environmental impact and carbon footprint. However, its practical application faces two major hurdles: salt crystallization at the evaporation interface and contamination of condensate by volatile organic compounds (VOCs), notably phenol. Herein, we present a floating photothermal-photocatalytic solar evaporator based on a hydrogel-sponge nanocomposite. The integration of hydrogel with sponge creates a unique biphasic heterogeneous structure, which establishes an inherent salt concentration gradient for long-term and efficient salt rejection (self-cleaning function). Simultaneously, the Schottky heterojunction formed between Ti3C2 MXene and BiOClI generates a strong interfacial electric field that drives efficient photocatalytic mineralization of phenol. The device operates stably for over 30 days in high-salinity wastewater (14 wt % NaCl, 10 mg L-1 phenol), producing freshwater without salt accumulation and with phenol residues below the detection limit. Under 1-sun illumination, it achieves an evaporation rate of 2.4 kg m-2 h-1 with an energy efficiency of 87.8%. Life cycle assessment confirms the significant environmental benefits of our SDZLD technology and estimates a treatment cost of approximately 7.75 EUR per ton of wastewater, which is about 50% lower than that of conventional evaporation pond methods. This work provides an innovative SDZLD-centered strategy to alleviate water scarcity, contributing toward UN Sustainable Development Goal 6.1.