julilili42/papers huggingface dataset:
Geometric immunosuppression in CAR T-cell treatment: Insights from mathematical modeling
2025-06-11

Chimeric antigen receptor T (CAR T) cell therapy has emerged as a promising treatment for hematological malignancies, offering a targeted approach to cancer treatment. Understanding the complexities of CAR T-cell therapy within solid tumors poses challenges due to the intricate interactions within the tumor microenvironment. Mathematical modeling may serve as a valuable tool to unravel the dynamics of CAR T-cell therapy and improve its effectiveness in solid tumors. This study aimed to investigate the impact of spatial aspects in CAR T therapy of solid tumors, utilizing cellular automata for modeling purposes. Our main objective was to deepen our understanding of treatment effects by analyzing scenarios with different spatial distributions and varying the initial quantities of tumor and CAR T-cells. Tumor geometry significantly influenced treatment efficacy in-silico, with notable differences observed between tumors with block-like arrangements and those with sparse cell distributions, leading to the concept of immune suppression due to geometrical effects. This research delves into the intricate relationship between spatial dynamics and the effectiveness of CAR T therapy in solid tumors, highlighting the relevance of tumor geometry in the outcome of cellular immunotherapy treatments. Our results provide a basis for improving the efficacy of CAR T-cell treatments by combining them with other ones reducing the density of compact tumor areas and thus opening access ways for tumor killing T-cells.
Outcome-associated factors in a molecularly defined cohort of central neurocytoma
2025-06-11

Abstract Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using atypical features and an elevated Ki67 proliferation index. However, these markers lack consistent definitions, raising the need for objective criteria. Genome-wide DNA methylation profiles were examined in 136 tumors histologically classified as CN. Clinical/histopathological characteristics were assessed in 93/90 cases, and whole-exome sequencing was conducted in 12 cases. Clinical and molecular characteristics were integrated into a survival model to predict progression-free survival (PFS). A diagnosis of CN was epigenetically confirmed in 125 of 136 cases (92%). No DNA methylation subgroups were identified, but global DNA hypomethylation emerged as a hallmark feature of CN associated with higher recurrence risk. Risk stratification based on histological features of atypia and Ki67 proliferation index was not reproducible across neuropathologists. Hypomethylation at the FGFR3 locus, accompanied by increased FGFR3 protein expression, was observed in 97% of cases. Gross total resection was associated with significantly improved PFS compared to STR, while patients undergoing STR receiving radiotherapy had a better outcome ( p = 0.0001). Younger patients were identified as having a higher risk of recurrence ( p = 0.026). Patient age and treatment strategy were key factors associated with survival outcomes in this cohort. These findings underscore the importance of closer follow-up for younger patients and radiotherapy for STR cases. Furthermore, FGFR3 represents a hallmark feature and potential therapeutic target, warranting further investigation.
High Diagnostic Performance of the Indicator Plaster Neuropad for the Detection of Established Diabetic Autonomic Neuropathy
2025-06-11

Aim: The aim of this study was to evaluate the specificity, sensitivity and accuracy of the Indicator Plaster Neuropad in detecting established Diabetic Autonomic Neuropathy (DAN). Methods: We studied 180 patients with Diabetes Mellitus (DM, mean age 49.5 ± 16 years, 82 with DM type 1). All patients underwent the following Cardiovascular Reflex Tests (CARTs): R-R variation during deep breathing (Mean Circular Resultant (MCR) and standard deviation (SD)), Valsalva maneuver, R-R variability after a rapid change from lying to standing position and postural hypotension. The presence of DAN was established if ≥2 CARTs were abnormal. According to the result the patients were divided into two groups, one with DAN and one without DAN. Assessment with Neuropad was performed also in all patients. Results: Abnormal perspiration with Neuropad (uncompleted or no change in color) was detected in 94 patients. Established DAN was detected in 85 patients. The sensitivity, specificity and accuracy of Neuropad for the diagnosis of established DAN were 87.1%, 78.9% and 82.8%, respectively and area under the curve was 0.846 and 95% CI (0.787, 0.905). Conclusions: Neuropad has high sensitivity, specificity, and accuracy in detecting established DAN, as defined by ≥2 abnormal CARTs.
Unleashing the power of CAR-M therapy in solid tumors: a comprehensive review
2025-06-12

Chimeric antigen receptor (CAR) macrophage therapy represents a promising new frontier in cancer immunotherapy, with the potential to overcome the limitations of CAR-T cell approaches, particularly in solid tumours. This comprehensive review focuses on the current state and future prospects of CAR macrophage technology, emphasising its applications in solid malignancies across preclinical and early clinical development. The key topics covered included CAR design optimisation, macrophage sources and engineering strategies, mechanisms of antitumour activity, in vivo efficacy in animal models, initial clinical trial results, and challenges for broader implementation. The unique properties of macrophages, including tumour penetration and microenvironment modulation, offer significant advantages over T cell-based therapies in solid-tumour settings. However, strategies to enhance persistence, maintain proinflammatory phenotypes, and improve manufacturing are required. Although early research suggests additional applications beyond oncology, including for infectious and inflammatory diseases, this review primarily concentrates on the oncologic potential of CAR-M therapies. Continued optimisation and larger randomised trials will be critical to establish clinical efficacy and define the role of this approach in the treatment of solid tumours.
Highly multiplexed molecular inversion probe panel in Plasmodium falciparum targeting common SNPs approximates whole-genome sequencing assessments for selection and relatedness
2025-06-12

Introduction The use of next-generation sequencing technologies (NGS) to study parasite populations and their response and evolution to interventions is important to support malaria control and elimination efforts. While whole-genome sequencing (WGS) is optimal in terms of assessing the entire genome, it is costly for numerous samples. Targeted approaches selectively enriching for the sequence of interest are more affordable and have higher throughput but sometimes lack adequate information content for key analyses. Methods We have developed a highly multiplexed molecular inversion probe (MIP) panel (IBC2FULL) targeting 4,264 single-nucleotide polymorphisms (SNPs) with ≥5% minor allele frequency (MAF) in Sub-Saharan African regions from publicly available Plasmodium falciparum WGS (n = 3,693). We optimized the panel alone and in combination with antimalarial drug resistance MIPs in laboratory P. falciparum strains at different parasitemias and validated it by sequencing field isolates from the Democratic Republic of Congo, Ethiopia, Ghana, Mali, Rwanda, Tanzania, and Uganda and evaluating the population structure, identity-by-descent (IBD), signals of selection, and complexity of infection (COI). Results The new panel IBC2FULL consisted of 2,128 MIPs (containing 4,264 common SNPs) spaced by 5.1–18.4 kb across the entire genome. While these microhaplotypes were developed based on variations from Sub-Saharan African WGS data, 59.3% (2,529) of SNPs were also common in Southeast Asia. The MIPs were balanced to produce more a uniform and higher depth of coverage at low parasitemia (100 parasites/μL) along with MIPs targeting antimalarial drug resistance genes. Comparing targeted regions extracted from public WGS, we observed that IBC2FULL provided a higher resolution of the local population structure in Sub-Saharan Africa than current PCR-based targeted sequencing panels. For sequencing field samples (n = 140), IBC2FULL approximated WGS measures of relatedness, population structure, and COI. Interestingly, genome-wide analysis of extended haplotype homozygosity detected the same major peaks of selection as WGS. We also chose a subset of 305 high-performing MIPs to create a core panel (IBC2CORE) that produced high-quality data for basic population genomic analysis and accurate estimation of COI. Discussion IBC2FULL and IBC2CORE panels have been designed to provide an improved platform for malaria genomic epidemiology and biology that can approximate WGS for many applications and is deployable for malaria molecular surveillance in resource-limited settings.
Deep learning-driven spectral exploration for metal-insulator-metal plasmonic metasurfaces
2025-06-12

Metal-insulator-metal plasmonic metasurfaces exhibit intricate spectral responses arising from the interplay among localized surface plasmon polaritons, surface lattice resonances, and Fabry-Pérot cavity modes. However, traditional characterization methods relying on iterative electromagnetic simulations and manual spectral analysis face inefficiencies in handling complex parameter spaces and measurement-condition heterogeneity. Here, we present a deep learning-driven framework to analyze the spectral behaviors of metal-insulator-metal metasurfaces by integrating experimental fabrication, finite-difference time-domain simulations, and data-driven spectral classification and regression. Gradient-parameter metasurfaces with varying insulator gaps (20–200 nm), nanostructure geometries (disc/ring), and periodicities (500–1500 nm) are fabricated via electron-beam lithography and optically characterized under reflection/transmission configurations. Numerical simulations reveal the interplay of hybridized modes and surface charge dynamics. Leveraging convolutional and recurrent neural networks (CNNs, LSTMs, GRUs) and Transformers, we achieve robust classification of 24 structural categories and spectral regression for inverse design. Notably, LSTM models attain superior classification accuracy (&gt;99.2%), while CNN demonstrates superior time efficiency. This work establishes a data-physics-integrated paradigm for rapid MIM metasurface characterization, and the proposed methodology bridges the gap between complex optical responses and deep learning-driven spectral exploration, advancing applications in label-free biosensing and tunable photonic systems.
Performance of molecular inversion probe DR23K and Paragon MAD4HatTeR Amplicon sequencing panels for detection of Plasmodium falciparum mutations associated with antimalarial drug resistance
2025-06-12

Abstract Background Molecular surveillance of drug-resistant Plasmodium falciparum is crucial for malaria control in endemic regions. Two targeted-resequencing tools, the Molecular Inversion Probe (MIP) drug resistance panel DR23K and the Multiplexed Amplicons for Drugs, Diagnostics, Diversity, and Differentiation using High-Throughput Targeted Resequencing (MAD 4 HatTeR) panel, are widely used to detect resistance genotypes. However, comparisons of their performance for genotyping drug resistance polymorphisms in malaria parasites and their comparative utility for other use cases is lacking. Methods To compare the performance of DR23K and MAD 4 HatTeR in terms of sequencing depth, sensitivity to minor alleles, and precision, each platform was used to evaluate SNP alleles and microhaplotypes in double- and triple-strain mixtures of well-characterized laboratory parasites at densities of 10, 100, 1000, and 10,000 parasites/μL. In addition, 67 Ugandan field samples collected in 2022 were genotyped using each platform to assess performance and concordance. Results Across the four parasite densities of 10, 100, 1000, and 10,000 parasites/μL, MAD 4 HatTeR exhibited superior sequencing depth (mean reads per locus: 144, 992, 1153, and 1300) compared to DR23K (mean unique molecular identifiers [UMIs] per locus: 1, 4, 49, and 364). For SNP detection, MAD 4 HatTeR achieved 100% sensitivity at 2% within-sample allele frequency (WSAF) at 1000 and 10,000 parasites/μL, whereas DR23K achieved 100% sensitivity at 40% and 5% WSAF at these densities, respectively. Microhaplotype sensitivity was lower for both assays; MAD4HatTeR reached 69% sensitivity at 10 parasites/μL when WSAF was ≥ 10%, increasing to 100% sensitivity at 2% WSAF and 100 parasites/μL. DR23K had &lt; 50% sensitivity at 10 and 100 parasites/μL. In field samples, which commonly contain polyclonal infections, high concordance was observed between the two methods for all SNPs (94%, 1848/1969) and polymorphic SNPs (88%, 898/1019). All discrepancies were attributed to varied detection of minority alleles in mixed genotype infections. Conclusions MAD 4 HatTeR demonstrated higher sensitivity than DR23K, particularly at low parasite densities. Both assays showed strong concordance for genotyping key resistance mutations in field samples, supporting their reliability. These findings suggest MAD 4 HatTeR as the preferred assay for low-density parasite studies and microhaplotype analysis, while DR23K may be appropriate for specific applications with high-parasite density samples, where detection of minority alleles is not prioritized, or when more comprehensive genome coverage is required.
Variability in the management of portal hypertension across European countries: A survey‐study by ESPGHAN Portal Hypertension Special Interest Group
2025-06-12

Abstract Portal hypertension (PHT) remains a significant burden in children with chronic liver disease (CLD) or portal vein thrombosis (PVT). Management strategies vary depending on the underlying cause and clinical presentation. There is a lack of consensus on various aspects of PHT, including the optimal approach to screening, prophylactic endoscopy and treatment, and pharmacological interventions. This brief communication summarizes the results of a recent questionnaire‐based study conducted by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Portal Hypertension Special Interest Group to explore current practices in the management of PHT among its members. Screening for the presence of varices and the approach to primary and secondary prophylaxis differ across Europe. The survey also demasked a high variability of both pharmacological and surgical management of PHT and highlights knowledge gaps and areas for future research.
Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis
2025-06-12

Background and objectives Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS). Methods Data were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up. Results 1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (−0.10 to 1.55) and NfL of 0.64 (−0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001). Conclusions GFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.
Fear of COVID-19, Physical Activity, and Psychopathology
2025-06-12

Abstract: Background: The COVID-19 pandemic was associated with high fear of infection and consequences of the pandemic, decline in physical activity and increase in depressive symptoms. Aims: This study assessed whether fear of COVID-19 is cross-sectionally associated with symptoms of depression in a clinical outpatient sample and if physical activity moderates this effect. Methods: Data was collected between March 2021 and May 2022 at 10 study sites in a cross-sectional assessment of 401 participants, aged 18–65 ( M = 42.08, SD = 13.26, 71.0% female). All participants fulfilled diagnostic criteria for major depressive disorders, insomnia, panic disorder, agoraphobia, or posttraumatic stress disorder. Data was analyzed using linear regression models including fear of COVID-19 (disease anxiety; consequence anxiety), self-reported physical activity, physical activity measured by accelerometers (min/week), as well as the interaction of these variables as predictors, depressive symptoms as the outcome. Results: The primary model’s fit was significant, F(15, 377.13) = 1.89, p = .022. Consequence anxiety was significantly and positively associated with depressive symptoms (β = 0.12, t = 2.33, p = .020). We further observed a negative association between self-reported physical activity and depressive symptoms (β = −0.15, t = −2.73, p = .007). There was no significant interaction effect. Limitations: These results should be interpreted as an observational association. Conclusion: Results show that fear of the consequences of COVID-19 was positively associated with depressive symptoms, but physical activity did not moderate this association. We report an independent, negative association between self-reported physical activity and depressive symptoms.
Combining country indicators and individual variables to predict soil-transmitted helminth infections among migrant populations: A case study from southern Italy
2025-06-13

An increase in global migration towards developed countries along with climate change has led to the occurrence of Neglected Tropical Diseases (NTDs) in otherwise non-endemic countries. In this paper we focus on Soil Transmitted Helminth (STH) infections which disproportionately affect people living in poverty in tropical regions. To reduce the threat of STHs in migrant populations living in non-endemic countries, diagnosis and treatment are paramount but also present logistical challenges. This study investigates how statistical modelling can be used to assist the identification of individuals infected with STHs. Specifically, we show how to combine individual variables (e.g., age, sex and time in Italy) with publicly available country indicators (Human Development Index, Multidimensional Poverty Index and Inequality-adjusted Human Development Index) which describe development in the migrant’s country of origin. We combine these indices and their factors in binomial mixed-effects models which can be used to predict the status of STH infections in migrant populations. By presenting a case study on migrants in southern Italy, we assess the relative importance of the individual-level variables and country-level indicators in enhancing the predictive power of the models. The results show that the country-level indices play a more important role but also highlight that individual data can help improve the model performance when combined with the former. To the best of our knowledge this is the first study investigating using country-level indicators to predict parasite infection status of migrants. Our study indicates that statistical models can play an important role in reducing the resources required to identify migrants requiring anthelmintic treatment against STHs and help to make statistically informed decisions.
Intravenous thrombolysis versus endovascular thrombectomy in acute basilar artery occlusion—A multicenter cohort study
2025-06-13

Background: Randomized controlled trials have demonstrated an improved outcome of basilar artery occlusion (BAO) with endovascular thrombectomy (EVT) compared to best medical treatment. However, a minority of the patients recruited up to 12–24 h from onset in the positive trials received intravenous thrombolysis (IVT), and a trial with a higher IVT rate did not show superiority of EVT. Thus, the efficacy and safety of EVT compared to IVT for BAO remain less clear. Aims: We aimed to compare outcomes after IVT alone to EVT with or without IVT for acute BAO. Methods: This international, observational, retrospective study included patients who received recanalization therapy for BAO at six centers between January 2010 and March 2024. The primary outcome was 3-month modified Rankin Scale (mRS) score 0–3, and secondary outcomes comprised mRS 0–2, ordinal mRS, mortality, and symptomatic intracranial hemorrhage. Outcomes after IVT versus EVT ± IVT were compared using inverse probability-weighted regression adjustment models adjusting for known predictors of outcome in BAO and baseline variables differing between the treatment groups. Interaction of the treatment group with symptom severity and onset-to-treatment time was tested. Results: Of 523 patients with BAO (median age 69, 35.2% women), 28.9% received IVT and 71.1% EVT ± IVT. The IVT-alone group had a lower baseline National Institutes of Health Stroke Scale score (median 11 vs 15) but equally extensive ischemic changes in baseline imaging. After inverse probability-weighted regression adjustment, the IVT-alone group had higher odds of mRS 0–3 (adjusted odds ratio (aOR) = 2.33 [95% confidence interval (CI) = 1.31–4.12]), mRS 0–2 (aOR = 1.93 [95% CI = 1.12–3.30]), lower median mRS (aOR = 1.81 [95% CI = 1.21–2.71]), and lower mortality (aOR = 0.53 [95% CI = 0.29–0.97]), but no difference in symptomatic intracranial hemorrhage (aOR = 0.81 [95% CI = 0.28–2.36]). No interactions for the primary outcome were found. Conclusion: In this study, patients with BAO had better outcome after IVT than EVT ± IVT independent of symptom severity and time from onset. Although the non-randomized design of the study warrants caution, the results encourage further trials comparing EVT and IVT to guide recanalization therapy in BAO patients. Data access statement: Anonymized data are available upon reasonable request to the corresponding author following the national legislation.
Mean square temporal error estimates for the two-dimensional stochastic Navier–Stokes equations with transport noise
2025-06-13

Abstract We study the two-dimensional Navier–Stokes equation with transport noise subject to periodic boundary conditions. Our main result is an error estimate for the time discretization showing a convergence rate of order (up to) 1/2. It holds with respect to mean square error convergence, whereas previously such a rate for the stochastic Navier–Stokes equations was only known with respect to convergence in probability. Our result is based on uniform-in-probability estimates for the continuous as well as the time-discrete solution exploiting the particular structure of the noise. Eventually, we perform numerical simulations for the corresponding problem on bounded domains with no-slip boundary conditions. They suggest the same convergence rate as proved for the periodic problem hinging sensitively on the compatibility of the data. We also compare the energy profiles with those for corresponding problems with additive or multiplicative Itô-type noise.