julilili42/papers huggingface dataset:
Cryopreservation of siRNA-Treated Cells Is Feasible
2025-09-23

Cryopreservation is a routine step in the manufacturing process of adoptive cell therapies (ACT), providing critical logistic flexibility. RNA interference (RNAi)-based therapies are increasingly being explored as enhancers or modulators of ACT. However, the impact of cryopreservation on cells treated with RNAi-based therapies has not been investigated before. In this study, we addressed this knowledge gap by examining silencing efficacy in small interfering RNA (siRNA)-treated cells that undergo cryopreservation. Our findings demonstrate that silencing in cryopreserved cells is comparable to that in cells maintained continuously in culture. Moreover, we found that the duration of siRNA exposure plays a significant role in cells that later undergo cryopreservation, with extended exposure improving silencing efficiency. However, this effect diminishes at higher siRNA concentrations. Additionally, we showed that siRNA treatment is feasible at low temperatures (2°C-8°C), and siRNA-treated cells can be cryopreserved for extended periods (at least 1 month) without loss of efficacy. Our work establishes the feasibility of integrating siRNA treatments into current manufacturing processes for ACT.
Tracking the emergence of the Upper Palaeolithic in western Asia and Europe: A Multiple Correspondence Analysis of Protoaurignacian and Southern Ahmarian lithics
2025-09-24

Reconstructing changes in human behaviour during the Pleistocene, particularly when based on lithic or other artefact types, is often hindered by the traditional categorisation of these materials into discrete entities. The Early Upper Palaeolithic of Mediterranean Eurasia – comprising the Protoaurignacian, Early Aurignacian, Northern Ahmarian, and Southern Ahmarian technocomplexes – represents the first emergence of a pan-European cultural unit. However, this conventional categorisation into discrete entities obscures a deeper understanding of the dynamics of Homo sapiens ’ dispersal across Eurasia during this period. In this study, we apply Multiple Correspondence Analysis (MCA) to assess patterns of reduction processes, technological variability, and inter-assemblage homogeneity across technocomplexes. Using the comprehensive dataset provided in this paper, we analyse variability by grouping it into three domains: platform preparation, convexity management, and retouch. Solutrean Upper Palaeolithic assemblages from the Iberian Peninsula are used as an outgroup. We selected blanks, retouched and unmodified ones, and we focused on blades and bladelets, which are the typical end-product of the Upper Palaeolithic knapping. We excluded cores to avoid pitfalls of late or early reduction patterns, as our blanks cover most of the knapping sequence. We applied MCA to Early Upper Palaeolithic blanks for the first time, providing a geographically widespread comparison. Our results show that the MCA of blank attributes, particularly those describing the preparation of convexities, is sufficiently robust to reveal the distinctiveness of Early Upper Palaeolithic technologies relative to Solutrean ones. Our analysis also confirms technological similarities between the Southern Ahmarian and the Protoaurignacian, particularly in bladelet production, reinforcing the interpretation of bladelets as a primary production target in Early Upper Palaeolithic lithic technology. This study contributes laying the foundation for open-access databases, standardised analytical protocols, and MCA to support efforts in understanding hominin dispersal and interaction during this pivotal phase of prehistory.
Engineering biomimetic tissue barrier models on chips: From design and fabrication to applications in disease modeling and drug screening
2025-09-24

Replicating the in vitro properties of tissue barriers-such as the blood-brain barrier, gut, skin, lung, kidney, retina, nasal epithelium, and placenta-is crucial for many applications, including drug screening, studying molecular transport, drug delivery, and disease modeling in preclinical studies. Organ-on-a-chip (OoC) platforms are advanced three-dimensional (3D) in vitro models that aim to replicate various aspects of organ functionality within microfluidic systems by providing microenvironments akin to native tissue. When used to model the interface between two different tissue compartments, OoC technology offers a promising platform for more accurately replicating the physiology and pathophysiology of various tissue barriers in the body. This review focuses on the state-of-the-art biomimetic tissue barrier models, ranging from two-channel tissue barrier-on-a-chip systems with a thin porous membrane to hydrogel-based membrane models. Specifically, it explores the engineering of tissue barrier-on-a-chip platforms, highlighting various fabrication techniques for microfluidic chips and membranes, as well as methods for functional characterization of the engineered tissue barriers. Additionally, we discuss the development of organ-specific barrier models and multi-organ-on-a-chip systems for studying inter-organ communication. Finally, we highlight the current challenges in the field and future directions in advancing tissue barrier modeling using OoC technology.
A haplotype-based evolutionary history of barley domestication
2025-09-24

Abstract Barley is one of the oldest cultivated crops, with a complex evolutionary and domestication history 1 . Previous studies have rejected the idea of a single origin and instead support a model of mosaic genomic ancestry 2,3 . With increasingly comprehensive genome data, we now ask where the haplotypes — the building blocks of this mosaic — originate, and whether all domesticated barleys share the same wild progenitors or whether certain wild populations contribute more heavily to specific lineages. To address these questions, we apply a haplotype-based approach to investigate the genetic diversity and population structure of wild and domesticated barley. We analyse whole-genome sequences from 682 genebank accessions and 23 archaeological specimens, tracing the spatiotemporal origins of haplotypes and identifying wild contributors during domestication and later gene flow events. Ancient DNA supports our genome-wide findings from modern samples. Our results suggest that a founding domesticated population emerged in the Fertile Crescent during a prolonged period of pre-domestication cultivation. A key practical insight is that the high haplotype differentiation among barley populations — arising independently, or layered on top, of selection — poses challenges for mapping adaptive loci.
Clinical data-driven classification of pre-frailty reveals sex-specific patterns – Data from the Berlin Aging Study II (BASE-II)
2025-09-24

Frailty is a geriatric condition with multidimensional consequences that strongly affect older adults' quality of life. The lack of a universal standard to describe, diagnose, and treat frailty further complicates this situation. Nowadays, multitudinous frailty assessment tools are applied depending on the regional and clinical context, adding complexity by increasing heterogeneity in the definition and characterization of frailty. Better insights into the causes and pathophysiology of frailty and its early stages are required to establish strong and accurately tailored treatment rationales for frail patients. We analysed participants aged 60 and above using cross-sectional biochemical and survey data from the Berlin Aging Study II (BASE-II, N=1512, pre-frail=470, frail=14), applying machine-learning techniques to investigate determinants of physical frailty measured by Fried et al.'s 5-item frailty phenotype. Our findings highlight new prognostic sex-specific biomarkers of pre-frailty (the early stage of frailty) with possible clinical applications, enriching the current sex-agnostic diagnostic scores with easy monitorable physical and physiological characteristics. Low appendicular lean mass and high fat composition in men, or vitamin D deficiency and high white blood cell counts in women, emerged as strong indicators of the respective pre-frailty profiles. Because the number of fully frail individuals was extremely small (n = 14, <1%), our findings should be interpreted as reflecting predictors of pre-frailty, not of frailty itself. We conclude that understanding the development of frailty remains a complex challenge, and that sex-specific differences must be considered by clinical geriatricians and researchers.
A historical–relational approach to governance through states of emergency: from spectacular to non-spectacular settings in Turkey
2025-09-25

Abstract States of emergency are usually approached separately in social, political, and economic policy spheres while they are generally tied to a concrete time frame: security, disasters, and economic crises are portrayed as discrete emergencies occupying specific periods. This paper shows that seemingly different and sometimes contradictory processes of states of emergency often intertwine with each other despite their variegated domains, scales, reasonings, and political endeavors. Moreover, their legacies and origins are found in the broader history of articulation of new forms of governance and accumulation of wealth. The paper presents two cases in Turkey that differ in terms of the violence they entailed while both exploited the same emergency declaration against disasters and the new Law No. 6306 on land grabbing. The first is a series of spectacular incidents in the southeastern Kurdish city of Diyarbakır and the second is an ethnographic study from Eskişehir, a mundane setting in western Anatolia. The study develops a historical–relational framework to examine how emergency governance operates through dual, interwoven logics of ruling and capital accumulation. This allows us to move beyond ready-made, reductionist understandings of contemporary emergency governance. Discerning institutionalization of states of emergency also shows their fragility and blurs the line between spectacular and non-spectacular.
PhyloNaP: a user-friendly database of Phylogeny for Natural Product–producing enzymes
2025-09-25

Abstract Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive and requires extensive knowledge about the specific enzymes. Existing resources rarely cover biosynthetic enzymes and lack the context needed for meaningful analysis. We present PhyloNaP, the first large-scale resource dedicated to phylogenies of biosynthetic enzymes. PhyloNaP provides ∼18,500 annotated and interactive trees enriched with chemical, functional, and taxonomic information. Users can classify their own sequences via phylogenetic placement, enabling functional inference in an evolutionary context. A contribution portal allows the community to submit curated trees. By combining scale, breadth of annotation, and interactive functionality, PhyloNaP fills a major gap in bioinformatics resources for enzyme discovery and annotation, with immediate applications to secondary metabolism and beyond. Availability https://phylonap.cs.uni-tuebingen.de
Intravenous Thrombolysis for Acute Central Retinal Artery Occlusion: Protocol For a Systematic Review and Individual Participant Data Meta-Analysis of Randomized Controlled Trials
2025-09-25

ABSTRACT Importance Central retinal artery occlusion (CRAO) is a disabling subtype of acute ischemic stroke. It is not known whether intravenous (IV) thrombolysis delivered within 4.5 hours of time last known well (LKW) improves visual outcomes. Study Design Systematic review and individual participant data meta-analysis. Objective The objective of this study is to determine whether IV thrombolysis improves visual outcomes among patients with acute non-arteritic CRAO when administered within 4.5 hours of time LKW compared with placebo, no IV thrombolysis, and/or anti-thrombotic therapy. Evidence Review Plan This study is prospectively registered through PROSPERO (#1154900). We will include randomized controlled trials (RCTs) that enroll patients with non-arteritic CRAO presenting within 4.5 hours of time LKW. We will not include non-controlled interventional studies or retrospective studies. We will search MEDLINE, Embase, the Cochrane Library, Web of Science, and the ClinicalTrials.gov registry from inception through the date of commencement of the systematic review. We will assess the risk of bias using the Cochrane Risk of Bias Tool 2.0. We will contact the corresponding author(s) of any studies identified that meet the study selection criteria. We will inspect, harmonize, and collate trial datasets. The primary end point will be attainment of a final best corrected visual acuity (BCVA) equal to or better than 20/63 (logarithm of the minimum angle of resolution [logMAR] of ≤0.5). Secondary end points will include shift analyses of key visual acuity outcome categories according to the World Health Organization (WHO) International Classification of Disease (ICD)-11, final BCVA considered as a continuous variable, final BCVA equal to or better than 20/100 (logMAR of ≤0.7), final BCVA equal to or better than 20/200 (logMAR of ≤1), a quantitative measure of visual field function (where available), global disability (modified Rankin Scale score [mRS]), and key safety end points (including symptomatic intracranial hemorrhage [sICH] and other systemic hemorrhage). We will fit a series of mixed logistic and linear regression models with trial, and trial by treatment interaction terms as random effects. To probe for sources of heterogeneity, we will pursue a series of subgroup and sensitivity analyses. Finally, a GRADE assessment will be presented. Conclusions and Relevance Completion of the proposed study will permit a synopsis of the interventional literature on IV thrombolysis for CRAO, generate a pooled estimate of the treatment effect, and allow exploration of sources of heterogeneity. Such results may be of interest to healthcare professionals, guideline development bodies, policymakers, payors, and future patients with CRAO. Funding Source An application for federal support from the US National Institutes of Health is planned. Registration This systematic review is prospectively registered: PROSPERO #1154900.
Real-World Evidence: Better than Nothing or the Future? A Perspective on Clinical Evidence Generation in Interventional Oncology
2025-09-25

Abstract Randomised controlled trials (RCTs) have traditionally been regarded as the gold standard in evidence-based medicine, providing a high level of evidence. However, mounting complexities, ranging from ethical issues and logistical barriers to rapid technological evolutions, have sparked interest in alternative or complementary evidence-generation methods. Real-world evidence (RWE) from large, well-designed research projects is increasingly viewed as powerful tools. Although RWE is sometimes perceived as “less robust” compared to RCTs due to potential biases, recent advances in study design, data capture, and analytical frameworks have highlighted its potential for shaping clinical practice and informing regulatory decisions. This article discusses the benefits and challenges of RWE within interventional oncology and explores whether it is merely “better than nothing” or indeed represents a key pillar of the future of clinical research.
Characterizing Gallium Dinitridocarbonates: A Focus on LiGa(CN2)2, Li13.6Ga2.8(CN2)10I2, and SrGa2(CN2)4
2025-09-25

This study describes the synthesis and characterization of three new gallium dinitridocarbonates: LiGa(CN 2 ) 2 , Li 13.6 Ga 2.8 (CN 2 ) 10 I 2 , and SrGa 2 (CN 2 ) 4 . These compounds are obtained through solid‐state metathesis reactions, demonstrating an efficient route for the formation of dinitridocarbonate‐based materials. The crystal structures of LiGa(CN 2 ) 2 and Li 13.6 Ga 2.8 (CN 2 ) 10 I 2 are solved and refined in the orthorhombic space groups I 2 1 2 1 2 1 and Imma , respectively. The single‐crystal diffraction study of SrGa 2 (CN 2 ) 4 revealed the monoclinic space group P 2 1 /c . All the compounds under consideration feature networks based on metal‐centered tetrahedral arrangements. The presence of lithium in the compounds LiGa(CN 2 ) 2 and Li 13.6 Ga 2.8 (CN 2 ) 10 I 2 is confirmed by 7 Li magic‐angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. Infrared spectroscopy measurements indicate the presence of carbodiimide and cyanamide units within the compounds. Furthermore, the optical reflectance of the air‐stable compound SrGa 2 (CN 2 ) 4 has shown to be a wide gap semiconductor.
Predicting the effect of individual weight-bearing on tibial load and fracture healing after tibial plateau fractures–introduction of a biomechanical simulation model
2025-09-25

Purpose The prescribed amount of weight-bearing after tibial plateau fractures is controversial because it affects osteosynthetic construct stability and fracture healing. We aim to introduce a simulation model that adequately predicts the effects of different weight-bearing amounts on stability and healing, based on the patient’s individual fracture pattern and treatment construct. Methods To safely test different amounts of weight-bearing limits, we first extracted knee joint forces for different weight-bearing limits from musculoskeletal simulation based on monitoring data of 22 uninjured participants. Correct loading was ensured with a force-measuring insole. We then tested three patients after tibial plateau fracture with their current weight-bearing level and constructed a simulation model determining implant stress, knee joint force, and fracture gap interfragmentary strain. The patient-specific weight-bearing level was then substituted for weight-normalized uninjured participant data to test different weight-bearing levels in the simulation model. Results The simulation model calculated individual construct stiffness and interfragmentary strain at different weight-bearing levels following the clinical course. When comparing the patient’s individual weight-bearing input with the weight-normalized input of the uninjured participants at the same level, comparable knee joint forces were extracted, showing the feasibility of this approach. Conclusion Using an adapted reference movement database, the model allows the determination of safe weight-bearing ranges concerning construct stability and fracture healing based on individual fracture morphology and treatment without exposing patients to excessive weight-bearing. Future studies can test this approach in more extensive patient-number studies and different treatment situations.
Real-world data of azacitidine for relapsed/refractory nodal T-follicular helper cell lymphoma in 11 patients
2025-09-25

Relapsed or refractory (r/r) nodal T-follicular helper cell lymphoma of the angioimmunoblastic type is a rare disease with a dismal prognosis. This disease usually harbors mutations in epigenetic modifiers. A standard of treatment for an r/r disease is not known. Here, we report real-world data of 11 patients with a median age of 73 years, treated with azacitidine, a hypomethylating agent. Overall survival was 182 days. Five patients died from progressive disease; three were in complete remission after allogeneic stem cell transplantation; two were in complete remission, still receiving azacytidine; and one was under treatment for relapse. The treatment was well-tolerated despite the advanced age, and there was a high burden of comorbidities with a median hematopoietic cell transplantation-specific comorbidity index (HCT-CI) of 5, a score for identifying relevant comorbidities. However, a grade 3 or 4 hematological toxicity occurred in nine patients. Azacitidine may be a suitable treatment option for some patients with r/r nodal T-follicular helper cell lymphoma.
Vision dominates sound in mediating classic cue-induced microsaccadic eye movement modulations in rhesus macaque monkeys
2025-09-25

Abstract Visual onsets in the environment cause a short-latency reduction in saccade generation likelihood. Concomitant with that, the metrics of the saccades that do happen near the time of saccadic inhibition reflect the landscape of stimulus-driven neural responses in topographically organized brain maps. While certain aspects of saccadic inhibition have already been explored from a neurophysiological perspective, several questions remain, including which sensory-motor pathways propagate visual input information to the final oculomotor control circuitry with such short latencies. Here, motivated by evidence of a dissociation between temporal and spatial aspects of saccadic inhibition, we devised behavioral paradigms experimentally manipulating either aspect. Rhesus macaque monkeys maintained gaze fixation, and we characterized visually-driven microsaccadic inhibition with and without paired auditory pulses. In one condition, the sound pulses were spatially-unbiased, thus only affecting the temporal processes associated with microsaccadic inhibition; in another, the pulses were spatially-biased, affecting both the temporal and spatial components. We found that sound pulses alone barely affected microsaccade rates. However, when paired with visual stimuli, they accelerated the timing of visually-driven microsaccadic inhibition by ∼14-18 ms. In terms of microsaccade directions, spatially-unbiased sounds interfered with, but did not eliminate, visually-driven direction modulations. Surprisingly, spatially-biased sounds had a much weaker effect on microsaccade direction modulations, even when the sound source was in the opposite hemifield as the appearing visual stimulus. We conclude that vision dominates sound in mediating classic microsaccadic inhibition, and we argue that our paradigms are ideal for neurophysiological investigations of the parallel sensory-motor pathways contributing to such inhibition. Significance Coordination of internal oculomotor eye movement plans with exogenous sensory events entails rapid resetting of the saccadic eye movement system, but the pathways mediating the resetting are unknown. We devised novel behavioral paradigms in primates, involving multisensory stimulation, which allow neurophysiological experiments to isolate the contributions of individual sensory, motor, and sensory-motor brain areas to saccadic resetting. Such paradigms underscore that resetting involves dissociable temporal and spatial processes that are dominated by the visual modality.
Augustinian Theology in the Hispano-Mozarabic Eucharistic Prayers of the Holy Week
2025-09-25

Abstract This article analyses Hispano-Mozarabic Eucharistic prayers in order to study the reception of Augustine’s theology. Especially, Augustine’s doctrine of the Trinity and his Christology were employed in the late 6th and 7th centuries to overcome Arianism . Thereby, several pivotal Augustinian formulations were dogmatised at the Councils of Toledo. These formulations were also adapted in the Hispano-Mozarabic Eucharistic prayers. Furthermore, these prayers also employ motifs and overarching concepts drawn from Augustine’s doctrine of grace. In this way, they emphasise the connection between sacramental theology and a theology of the cross. However, other aspects of Augustine’s soteriology, particularly his doctrine of predestination or his terminology of gracious grace, are largely neglected. Thus, these Eucharistic prayers contain a broad and condensed form of Augustine’s theology. This illustrates how a reciprocal relationship between the lex credendi and the lex orandi shaped the development of Augustinianism .