julilili42/papers huggingface dataset:
An inter-rater variability study between human and automatic scorers in 5-s mini-epochs of sleep
2025-02-07

While mini-epoch scoring agreement was generally high, it was still lower than within epochs, likely due to a lack of standard mini-epoch scoring procedure and the automatic classifier being trained on epochs. However, stage discrepancies between epochs and mini-epochs and increased stage shifting in mini-epochs support that epochs can contain several stages, and that mini-epochs could supplement more detailed sleep characterization potentially enabling more precise diagnosis and finding new polysomnographic biomarkers. Future studies should include larger datasets to refine mini-epoch scoring rules and exploit automatic classifiers e.g. via transfer learning.
Principled PCA separates signal from noise in omics count data
2025-02-07

Abstract Principal component analysis (PCA) is indispensable for processing high-throughput omics datasets, as it can extract meaningful biological variability while minimizing the influence of noise. However, the suitability of PCA is contingent on appropriate normalization and transformation of count data, and accurate selection of the number of principal components; improper choices can result in the loss of biological information or corruption of the signal due to excessive noise. Typical approaches to these challenges rely on heuristics that lack theoretical foundations. In this work, we present Biwhitened PCA (BiPCA), a theoretically grounded framework for rank estimation and data denoising across a wide range of omics modalities. BiPCA overcomes a fundamental difficulty with handling count noise in omics data by adaptively rescaling the rows and columns – a rigorous procedure that standardizes the noise variances across both dimensions. Through simulations and analysis of over 100 datasets spanning seven omics modalities, we demonstrate that BiPCA reliably recovers the data rank and enhances the biological interpretability of count data. In particular, BiPCA enhances marker gene expression, preserves cell neighborhoods, and mitigates batch effects. Our results establish BiPCA as a robust and versatile framework for high-throughput count data analysis.
The offensive role of the Bacillus extracellular matrix in driving metabolite-mediated dialogue and adaptive strategies with pathogenic fungi
2025-02-07

Abstract Bacterial□fungal interactions have traditionally been attributed to secondary metabolites, but the role of the bacterial extracellular matrix (ECM) in shaping these relationships has remained unclear. Here, we demonstrate that the ECM protein TasA is a key mediator in the antagonistic interaction between Bacillus subtilis and Botrytis cinerea . TasA enables Bacillus to tightly adhere to fungal hyphae, disrupts the β-glucan layer, and compromises fungal cytoskeletal integrity synergistically with fengycin, which causes cytological damage. Additionally, TasA acts as a carrier for bacillaene, amplifying its fungistatic activity. In response, B. cinerea mounts a multifaceted defense, enzymatically degrading fengycin, producing antibacterial oxylipins, and activating adaptive programs such as hyphal branching and chlamydospore formation. Our findings reveal the previously unrecognized role of ECM components in fungal suppression and the modulation of fungal adaptive responses. This study reveals the complex interplay between microbial aggression and defense, providing new insights into the ecological dynamics of microbial competition and coexistence.
A Walk into Space-Timeless Philosophy
2025-02-07

Abstract This article argues that Plato instrumentalizes the setting of the Phaedrus — conceptualized as a uniquely designed ‘chronotope’—to delineate his understanding of philosophy, and to intensify the dialogue’s intra- and extra-fictional pedagogical impact. The analysis especially of the prologue (227a1-230e5) shall show that (1) the walk out of town ( ἔξω τείχους ) symbolizes Phaedrus’ transgression from Sophistic rhetoric to Platonic philosophy; (2) the interlocutors’ interaction in and with their spatiotemporal environment throughout the prologue negotiates their reciprocal “teacher-student” relationship; (3) more specifically, Socrates’ stylization of the plane setting both establishes a proper epistemic method, and subjugates the investigation of external phenomena ( τὰ ἀλλότρια ) to the philosophical search for self-knowledge; (4) finally, the contextual inappropriateness of this stylization raises the question of where to situate the philosopher in their sociopolitical and cosmic context: they seem in many ways ἄτοπος , neither confined to any particular spatiotemporal environment nor interlocutor, simultaneously most out of place and universally at home.
Psychotherapy in patients with long/post-COVID – A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions
2025-02-08

Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in large-scale confirmatory trials.
Rethinking Professional Development: Development and Evaluation of an Evidence-Based Online PD Course on the Effective Use of Technology in the Classroom
2025-02-08

Technology-enhanced teaching (TET) is most effective when integrated meaningfully into classroom settings. Teachers require technological pedagogical knowledge (TPK) to achieve this integration. This study details the development and evaluation of an online professional development (OPD) course aimed at enhancing teachers’ TPK for the effective use of technology in science and language subjects. The course was created to rethink OPD, i.e., to overcome known shortcomings of OPD design consciously. It was based on the Interactive–Constructive–Active–Passive (ICAP) framework, which promotes interactive and constructive learning activities. Thus, the OPD course incorporated text-based and video-based interactive learning modules (learning nuggets), discussions about staged video vignettes showing classroom situations with conventional vs. good use of technology by the teacher, professional learning communities, and practical teaching trials with group reflections. The evaluation study of this OPD followed a pre–post design involving 76 in-service teachers. Participants completed surveys and a test of their ability to apply ICAP knowledge to teaching situations before and after the OPD. The evaluation revealed that teachers perceived the course as beneficial, though no statistically significant improvement in applied ICAP knowledge was observed. These findings highlight opportunities and challenges in designing and measuring effective OPDs that support the meaningful integration of technology into classroom practice.
Predictive Factors for Risk of Reinfection in Septic Two-Stage Revision of Total Hip and Knee Arthroplasties
2025-02-08

Background: The two-stage septic exchange is the most common therapy concept in the treatment of periprosthetic hip and knee infections. However, before the second-stage reimplantation can be carried out, the physician has to assess whether or not the eradication of the periprosthetic joint infection (PJI) has been successful. Therefore, the aim of this study was to evaluate possible predictive parameters for the successful treatment of PJI before and at the time of reimplantation. Methods: This study investigated a total of 145 patients with periprosthetic hip infection and 93 patients with periprosthetic knee infection, who all underwent a two-stage septic exchange between 2017 and 2021. In order to identify possible risk factors for reinfections, the patients underwent preoperative examination of serological inflammatory parameters, microbiological and histological examination of the periprosthetic membrane at the time of reimplantation, as well as postoperative evaluations at regular intervals for a period of at least 24 months. Results: During the follow-up period, reinfection occurred in 11.3% of cases after the two-stage septic revision. None of the serological, microbiological, or histological parameters were able to significantly predict the risk of reinfection. Risk factors associated with reinfection were BMI and previous revision surgery. Conclusions: Currently, there is no reliable predictive factor indicating the risk of reinfection at the time of reimplantation. New diagnostic methods need to be developed to evaluate the possibility and timing of endoprosthesis reimplantation.
Photoreceptor degeneration has heterogeneous effects on functional retinal ganglion cell types
2025-02-09

Abstract Retinitis pigmentosa is a hereditary disease‐causing progressive degeneration of rod and cone photoreceptors, with no effective therapies. Using rd10 mice, which mirror the human condition, we examined its disease progression. Rods deteriorate by postnatal day (P) 45, followed by cone degeneration, with most photoreceptors lost by P180. Until then, retinal ganglion cells (RGCs) remain light‐responsive under photopic conditions, despite extensive outer retinal remodelling. However, it is still unknown if distinct functional RGC types alter their activity or are even lost during disease progression. Here, we asked if and how the response diversity of functional RGC types changes with rd10 disease progression. At P30, we identified all functional wild‐type RGC types also in rd10 retinae, suggesting that at this early degenerative stage, the full breadth of retinal output is still present. Remarkably, we found that the fractions of functional types changed throughout progressing degeneration between rd10 and wild‐type: responses of RGCs with ‘Off’‐components (‘Off’ and ‘On–Off’ RGCs) were more vulnerable than ‘On’‐cells, with ‘Fast On’ types being the most resilient. Notably, direction‐selective RGCs appeared to be more vulnerable than orientation‐selective RGCs. In summary, we found differences in resilience of response types (from resilient to vulnerable): ‘Uncertain’ &gt; ‘Fast On’ &gt; ‘Slow On’ &gt; ‘On–Off’ &gt; ‘Off’. Taken together, our results suggest that rd10 photoreceptor degeneration has heterogeneous effects on functional RGC types, with distinct sets of types losing their characteristic light responses earlier than others. This differential susceptibility of RGC circuits may be of relevance for future neuroprotective therapeutic strategies. image Key points Retinitis pigmentosa is a hereditary disease causing progressive degeneration of rod and cone photoreceptors, with no effective therapies; it can be investigated using mutant mouse models, like rd10 , that mirror the human condition. Recent studies found that retinal ganglion cells (RGCs) in rd10 remain light‐responsive, despite extensive loss of photoreceptors and outer retinal remodelling; however, specific RGC types still may change or even lose their functional response profile during early degeneration. Using two‐photon calcium imaging, we assessed if and how the light‐evoked activity of RGCs, and, hence, the retinal output to the brain, differs during the disease progression in rd10 compared to wild‐type mice. We found differences in the resilience of functional RGC types: generally, ‘On’‐types were more resilient than ‘On–Off’ or especially ‘Off’ types. Our data suggest that interventions may be more effective in the ‘On’ pathways, which turned out to be more resilient in rd10 .
EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).
2025-02-10

664 Background: EV-302 /KEYNOTE-A39 (NCT04223856) demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit with first-line (1L) EV+P vs chemo in patients (pts) with la/mUC. EV+P is the standard of care (SOC) in global treatment guidelines for pts with untreated la/mUC. We present 12 mo of additional follow-up for EV-302 (&gt;2 y of median follow-up) and an exploratory analysis of pts with confirmed complete response (cCR). Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 and 8; IV) and P (200 mg; Day 1; IV) or gemcitabine with cisplatin or carboplatin every 3 wks. Dual primary endpoints were PFS by blinded independent central review (BICR) and OS. Select secondary endpoints were confirmed objective response rate (cORR), duration of response (DOR), and safety. An exploratory analysis evaluated treatment outcomes and safety in pts with cCR. Results: 886 pts were randomized to receive EV+P (n=442) or chemo (n=444). At data cutoff (Aug 8, 2024), median follow-up was 29.1 mo (95% CI, 28.5-29.9). PFS by BICR (HR, 0.48 [95% CI, 0.41-0.57]) and OS (HR, 0.51 [95% CI, 0.43-0.61]) were improved in the EV+P vs chemo arms (Table). OS benefit was seen irrespective of cisplatin eligibility or presence of liver metastases (mets). In the response-evaluable set, cORR was 67.5% for EV+P and 44.2% for chemo. Median DOR was 23.3 mo (95% CI, 17.8-not estimable [NE]) for EV+P and 7.0 mo (95% CI, 6.2-9.0) for chemo. 30.4% of pts in the EV+P arm and 14.5% in the chemo arm achieved cCR. Median duration of cCR was not reached for EV+P and 15.2 mo (95% CI, 10.3-NE) for chemo. Grade ≥3 treatment-related (TR) adverse events (AEs) in the EV+P vs chemo arms occurred in 57.3% vs 69.5% of pts in the safety analysis set (Table) and 61.7% vs 71.9% of pts in the cCR subgroup, respectively. TR deaths occurred in 1.1% vs 0.9% of pts in the safety analysis set in the EV+P vs chemo arms, respectively; none occurred in the cCR subgroup. Conclusions: EV+P continues to demonstrate superior efficacy vs chemo in a broad population, consistent with the primary analysis. Results confirm durable EV+P efficacy with no new safety signals, reinforcing EV+P as SOC for the 1L treatment of pts with la/mUC. Clinical trial information: NCT04223856 . Key efficacy and safety outcomes. EV+P Chemo EV+P vs chemo Efficacy (intent to treat set) n mo n mo HR (95% CI) Median PFS 442 12.5 (95% CI, 10.4-16.6) 444 6.3 (95% CI, 6.2-6.5) 0.48 (0.41-0.57) Median OS 442 33.8 (95% CI, 26.1-39.3) 444 15.9 (95% CI, 13.6-18.3) 0.51 (0.43-0.61) Cisplatin eligible 244 36.7 234 18.7 0.54 (0.42-0.70) Cisplatin ineligible 198 25.6 210 12.7 0.50 (0.39-0.64) Liver mets present 100 19.1 99 10.1 0.56 (0.40-0.78) Liver mets absent 342 39.3 345 18.3 0.50 (0.40-0.62) Safety (safety analysis set) n n Grade ≥3 TRAE 440 252 (57.3%) 433 301 (69.5%) –
Hepatitis E Virus Infection in Vietnamese Pregnant Women with Hepatitis B: Prevalence and Clinical Outcomes
2025-02-10

Abstract Background Hepatitis E virus (HEV) infection during pregnancy is associated with obstetric complications and adverse maternal and neonatal outcomes. This study aimed to determine the seroprevalence of HEV and RNA positivity in both healthy pregnant women and women coinfected with hepatitis B virus (HBV). Methods A cross-sectional study was conducted involving 528 pregnant women (278 with and 250 without hepatitis B surface antigen [HBsAg]) in their third trimester. Anti-HEV specific immunoglobulin (Ig) G and IgM antibodies were tested for using enzyme-linked immunosorbent assay, while HEV RNA was detected by means of nested polymerase chain reaction. The status of anti-HEV antibodies was analyzed regarding pregnancy outcomes and the risks of obstetric complications. Results The results indicated that 24% of participants (127 of 528) tested positive for anti-HEV IgG, while 2.5% (13 of 528) showed detectable anti-HEV IgM. Among HBV-positive women, 26% (55 of 250) had anti-HEV IgG, comparable to 22% (61 of 278) in HBV-negative controls. Notably, 28% (140 of 501) of cord blood samples were positive for anti-HEV IgG. No cases of HEV RNA were detected. The prevalence of anti-HEV IgG increased with maternal age and was associated with higher infant birth weights. Anti-HEV IgM positivity was associated with an increased risk of neonatal infections (odds ratio, 20.6; P = .05). Among HBsAg-positive women, those with anti-HEV IgG (26%) had higher gestational age at delivery and higher infant birth weights but lower platelet counts and prothrombin times (P &amp;lt; .05). Conclusions These findings highlight the endemic nature of HEV in Vietnam and underscore the potential risks of coinfection with HBV during pregnancy, which may lead to adverse obstetric outcomes.
Metabolic PCTA-Based Shift Reagents for the Detection of Extracellular Lactate Using CEST MRI
2025-02-10

Lactate is a key metabolic driver in oncology and immunology. Even in the presence of physiological oxygen levels, most cancer cells upregulate anaerobic glycolysis, resulting in abnormal lactate production and accumulation in the tumor microenvironment. The development of more effective, sensitive, and safe probes for detecting extracellular lactate holds the potential to significantly impact cancer metabolic profiling and staging significantly. Macrocyclic-based PARACEST agents have been reported to act as shift reagents (SRs) and detect extracellular lactate via chemical exchange saturation transfer (CEST) MRI. Here, we introduce a new family of SRs based on the PCTA ligand, an inherently stable and kinetically inert group of molecules with the potential for (pre)clinical translation. We observed that Yb-PCTA and Eu-PCTA can significantly shift lactate -OH signals in the CEST spectra. <i>In vitro</i>, CEST MRI experiments proved that imaging extracellular lactate specifically with these complexes is feasible even in the presence of competing small metabolites in blood and in the tumor microenvironment. <i>In vivo</i> preclinical imaging showed that Yb-PCTA can be safely administered intravenously in mice to detect extracellular lactate noninvasively. This work contributes to the field of precision imaging in medicine and provides evidence that the PCTA-ligand is a valuable scaffold for developing molecular and metabolic imaging sensors.
Enfortumab vedotin plus pembrolizumab in metastatic urothelial carcinoma: First results on outcomes and safety in a German multicenter real-world patient cohort (GUARDIANS).
2025-02-10

715 Background: The prospective phase 3 study EV-302 demonstrated superiority regarding efficacy of Enfortumab vedotin plus Pembrolizumab (EVP) compared to platinum-based chemotherapy in patients (pts) that received first-line (1L) therapy for metastatic urothelial carcinoma (mUC). Since presentation of the data in September 2023 EVP was considered a new standard of care (SOC) however only approved in Europe in August 2024. We analyzed efficacy and safety outcomes of pts treated with EVP outside of clinical trials. Methods: Retrospective data were collected from 19 German academic and community hospitals for pts with metastatic UC who received EVP as off-label therapy when reimbursed by their insurance company before European Medicines Agency (EMA) approval, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Median progression-free survival (mPFS) and overall survival (mOS) were estimated using the Kaplan-Meier method by local investigators. Results: We identified 215 pts for the safety cohort (all pts who received EVP at least once) and 164 pts for the efficacy cohort (all pts who received at least one staging or died prior to first planned imaging).The median age for the eligible patients was 71 yr (range 25-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown for 46.0/31.6/17.2/4.7/0.5% of patients. The overall response rate was 60.7% (partial response 51.0%, complete response 9.7%). mOS was not reached and mPFS was 13 mo (95% confidence interval 4.5-21.5). Any-grade AEs were observed in 73.0% and CTCAE grade ≥3 AEs in 30.2%. Any-grade immune-related AEs were observed in 37.7% and CTCAE grade ≥3 AEs in 16.7%. The most common AEs were peripheral sensory neuropathy (all grade: 30.2%) and skin toxicity (all grade:24.2%). No treatment-related fatal event occurred. Limitations include the retrospective design and short follow-up. Conclusions: Administration of EVP in a real-world patient population showed promising effectiveness and an acceptable toxicity profile. No new safety signals were reported. Our results support the use of EVP in 1L in pts with mUC. Updated data with longer follow-up will be presented at the meeting.
The effect of fasting on human memory consolidation
2025-02-10

The consolidation of long-term memory is thought to critically rely on sleep. However, first evidence from a study in Drosophila suggests that hunger, as another brain state, can benefit memory consolidation as well. Here, we report two human (within-subjects crossover) experiments examining the effects of fasting (versus satiated conditions) during a 10-hour post-encoding consolidation period on subsequent recall of declarative and procedural memories in healthy men. In Experiment 1, participants (n = 16), after an 18.5-hour fasting period, encoded 3 memory tasks (word paired associates, a visual version of the Deese-Roediger-McDermott task, finger tapping) and subsequently either continued to fast or received standardized meals. Recall was tested 48 h later in a satiated state. Experiment 2 (n = 16 participants) differed from Experiment 1 in that a What-Where-When episodic memory task replaced the Deese-Roediger-McDermott task and recall was tested only 24 h later in a fasted state. Compared with the satiated state, fasting enhanced cued recall of word paired associates (more correct and faster responses) and item recognition in the What-Where-When task. By contrast, fasting impaired recall of episodic context memory, i.e., spatial context in the Deese-Roediger-McDermott task, and temporal-spatial context in the What-Where-When task. Procedural memory (finger tapping) remained unaffected. This pattern suggests a differential effect of fasting selectively promoting consolidation of semantic-like representations in cortical networks whereas hippocampal representations of episodic context are weakened. We speculate that hunger strengthens cortical representations by suppressing hippocampal interference during wake consolidation. Yet, the underlying mechanism remains to be clarified.