julilili42/papers huggingface dataset:
Indirect Treatment Comparison between Ribociclib Combined with Non-Steroidal Aromatase Inhibitors and Ovarian Function Suppression vs. Tamoxifen in Premenopausal Women with Early Breast Cancer
2025-04-04

Abstract This study provides an indirect treatment comparison of ribociclib combined with non-steroidal aromatase inhibitors and ovarian function suppression (ribociclib + NSAI + OFS) vs. a frequently used treatment option in German clinical routine (tamoxifen ± OFS) in premenopausal patients with HR-positive (HR+), HER2-negative (HER2−) early breast cancer (BC). Data on premenopausal women treated with ribociclib and tamoxifen were derived from the NATALEE clinical trial (NCT03701334) and the retrospective German data collection CLEAR-B, respectively. NATALEE trial eligibility criteria were applied to the CLEAR-B dataset. Standardized mortality ratio weights were used for propensity score (PS) adjustment to balance study populations. All hazard ratios (HR) were calculated based on a 4-year-observation period for both treatment arms. Effectiveness endpoints comprised invasive and distant disease-free survival (iDFS, dDFS), recurrence-free survival (RFS), and overall survival (OS). Safety-related endpoints were treatment termination (TT) and toxicity-related TT (TTtox). For safety comparisons, the ribociclib arm was divided into groups that discontinued ribociclib + NSAI + OFS or ribociclib only. Significant beneficial effects favoring ribociclib + NSAI + OFS (n = 1115) over tamoxifen ± OFS (n = 822) were observed for all effectiveness outcomes (iDFS [HR = 0.5 (95% CI 0.35; 0.71); p &lt; 0.01]; dDFS [HR = 0.52 (95% CI 0.35; 0.77); p = 0.01], RFS [HR = 0.42 (95% CI 0.29; 0.62); p &lt; 0.01], OS [HR = 0.34 (95% CI 0.18; 0.63); p = 0.01]) during the 4-year-observation period. The effect of early treatment discontinuation showed no significant differences between ribociclib + NSAI + OFS and tamoxifen ± OFS (TT-a: HR = 1.2 [95% CI: 0.71; 2.01], p = 0.48; TTtox-a: HR = 0.54 [95% CI 0.22; 1.30], p = 0.23). In this retrospective analysis, ribociclib + NSAI + OFS demonstrated advantages across all effectiveness endpoints, including OS, in premenopausal women with HR+, HER2− early BC, without increasing overall treatment discontinuation rates compared to tamoxifen ± OFS.
Parental Phubbing and Adolescent Depression: The Role of Parental Involvement and Adolescent Grit
2025-04-04

Phubbing has become a widespread phenomenon in the era of mobile Internet. The Phubbing behavior in parent-adolescent relationships and its effects are gaining increasing academic attention. This study aimed to explore the mediating role of parental involvement between parental phubbing and adolescent depression, as well as the moderating role of grit in this relationship. Participants were 670 high school students (390 girls, 58.2%), aged 13 ∼ 19 years (<i>M</i> = 15.73, <i>SD</i> = 0.92). A questionnaire measuring parental phubbing, parental involvement, adolescent grit, adolescent depression, and demographic information was completed by the students on computers. Results showed that parental phubbing exerted an influence on adolescent depression through parental involvement and that the second stage of this mediation process was moderated by adolescent grit. For adolescents with higher grit, the negative association between parental involvement and adolescent depression was weaker. This study sheds light on the mechanism of how parental phubbing is related to adolescent depression and the role of positive adolescent characteristics in this association. Our findings may be useful for designing targeted prevention and intervention programs to reduce adolescent depression symptoms.
Easy scalable, low-cost open-source magnetic field detection system for evaluating low-field MRI magnets using a motion-tracked robot
2025-04-05

Abstract Objective Low-field magnetic resonance imaging is currently developing into a valuable diagnostic tool due to its simplicity of magnet array designs. Particularly, this allows the development of scanners as part of educational workshops, thus ensuring knowledge transfer and empowering local scientists to design tailored solutions for specific local problems. To obtain the maximum performance, the magnet needs to be shimmed requiring an automated system measuring the spatial magnetic field distribution. Methods A self-designed measuring probe based on commercial integrated Hall sensor chips is used and optimized by calibrating it in an easy-to-build calibration system. For positioning of the sensor, a low-cost five-degree-of-freedom robot arm is used and improved by camera-based motion tracking for precise localization of the sensor. Results The system is able to map the field of a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>45</mml:mn> <mml:mtext>mT</mml:mtext> </mml:mrow> </mml:math> -Halbach desktop MR magnet, as well as a self-designed x-gradient (used inside the magnet) with an efficiency of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>2</mml:mn> <mml:mtext>mT</mml:mtext> <mml:mo>/</mml:mo> <mml:mtext>m</mml:mtext> <mml:mo>/</mml:mo> <mml:mtext>A</mml:mtext> </mml:mrow> </mml:math> . The built-up Hall sensor demonstrates a level of precision that is competitive with commercial sensors. The entire positioning system can be freely scaled to accommodate larger designs by adjusting the kinematics. Conclusion The presented system is demonstrated to be comparable to already established measurement systems, while the costs, setup times, and mapping duration are greatly reduced.
Trends in Overall Survival in Lung Adenocarcinoma with EGFR Mutation, KRAS Mutation, or No Mutation
2025-04-05

Background: Treatment of lung adenocarcinoma has changed and now includes checkpoint inhibitors (CPIs) or, in the case of an EGFR mutation, third-generation EGFR TKI osimertinib. Few data compare the long-term overall survival (OS) of current and historic subgroups. Methods: This real-world analysis (KOMPASS study) included stage IV lung-adenocarcinoma patients with either EGFR, KRAS, or no mutation. Patients were assigned to the “current” EGFR, KRAS, or no-mutation cohort if they had mutation testing using NGS (n = 199; median date of diagnosis 2021). If they had an EGFR PCR test only, they were assigned to the “historic” EGFR or no-mutation cohort (n = 127; median date of diagnosis 2014). Results: Both the current and the historic EGFR cohorts had significantly longer OS than the respective no-mutation cohorts (HR 0.58 and 0.60, respectively). The current no-mutation and EGFR cohorts had a strong trend to longer OS than the respective historic cohorts. In the no-mutation cohorts, the improvement was due to an increase in long-term survivors (HR 0.71), whereas in the EGFR mutation cohorts, the median OS was improved without long-term survivors (HR 0.70). The KRAS cohort showed OS like the no-mutation cohort, with a plateau of long-term survivors around 20%. Conclusions: A comparison of our data with that of the phase III trials KEYNOTE-189 and FLAURA suggests that the improved outcomes are due to the use of CPIs or osimertinib. The clinical trial results are well translated into real-world clinical practice with comparable OS. KRAS patients benefit from CPI treatment like no-mutation patients.
Vaccination Against RhoC in Prostate Cancer Patients Induces Potent and Long-Lasting CD4+ T Cell Responses with Cytolytic Potential in the Absence of Clinical Efficacy: A Randomized Phase II Trial
2025-04-05

Background: A previous phase I/II study demonstrated potent and long-term immune responses in men with prostate cancer following vaccination with a 20mer synthetic peptide (RV001) derived from the Ras homolog gene family member C protein (RhoC). Moreover, a fraction of patients experienced prostate-specific antigen (PSA) responses, which prompted the initiation of a phase II double-blind randomized trial (NCT04114825). The primary endpoint was to study whether vaccination could postpone PSA progression. Furthermore, the study included an evaluation of vaccination-induced immune responses, and in-depth in vitro studies of RhoC-specific CD4+ T cell responses. Methods: Men with non-metastatic biochemical recurrence after either radical prostatectomy or radiation therapy were eligible for the study. Participants were randomized 1:1 to either subcutaneous injections of 0.1 mg/mL RV001 emulsified in Montanide ISA 51, or a placebo. Vaccinations were administered every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. Blood samples were collected from a subset of patients (n = 38) over the course of vaccination, and peripheral blood mononuclear cells (PBMCs) isolated for immunological assessment of vaccine-induced immune responses. Experiments using PBMCs from a healthy donor and a patient were performed to study the phenotype and function of RV001-specific CD4+ T cells. Results: A total of 192 men entered the study. There was no difference in time to PSA doubling, with 7.5 versus 9.3 months, or in time to initiating further therapies, 11.2 versus 17.6 months for treatment and control groups, respectively. At long-term follow-up, 12.9% of the patients in the vaccination arm had developed metastasis compared to 12% in the placebo arm. No serious treatment-related side effects were observed, and treatment-related adverse events did not differ between groups. Immunological examinations in a subset of patients demonstrated that the vaccination induced potent, long-lasting CD4+ T cell responses capable of proliferation and cytokine production. RV001-specific CD4+ T cells were shown to mediate cytotoxicity against a RhoC-expressing cancer cell line in an HLA-class II-dependent manner. Conclusions: Men randomized to active treatment with RV001V demonstrated the induction of potent, functionally capable, anti RhoC-CD4+ T cell responses. However, there was no benefit in time to biochemical progression, and no difference in time to the initiation of second-line therapies.
Risk stratification using the Merlin Assay (CP-GEP) in an independent cohort of 930 patients with clinical stage I/II melanoma who did not undergo sentinel lymph node biopsy
2025-04-06

This study shows that CP-GEP has the potential to stratify patients with early-stage melanoma who did not undergo SLNB based on their risk of recurrence. Patients with CP-GEP Low Risk have a significantly better long-term survival. CP-GEP shows to be promising for guiding SLNB referral and may support melanoma care by optimizing personalized treatment plans and potential surveillance regimens.
Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution
2025-04-06

Abstract Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in treating relapsed and refractory (R/R) B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Despite its success, the long-term effects and sequelae of CAR T cells on the immune system remain underexplored. This study presents a 1-year follow-up analysis of 52 patients (42 with R/R DLBCL and 10 with R/R MM) treated with anti-CD19– and B-cell maturation antigen-targeted CAR T cells, focusing on immune reconstitution and infectious complications. Our findings reveal that CAR T-cell therapy leads to profound depletion of B and T cells. CD4+ T cells and CD19+ B cells exhibited impaired regeneration after treatment. Infections were more frequent during the first 30 days. In the short-term follow-up, density of infections within 100 days at risk was 1.8 in patients with DLBCL and 4.6 in patients with MM, with bacterial infections predominating in this early period after CAR T-cell infusion. In addition, we observed a shift to viral infections in the long-term follow-up, alongside with a decline in infection density to 0.1 in patients with DLBCL and 0.4 infections per 100 days at risk in patients with MM, respectively. Severe cytokine release syndrome was associated with a higher risk of late-onset infections. These findings highlight the importance of close monitoring and prophylactic measures in patients undergoing CAR T-cell therapy to reduce infection risks and enhance immune recovery.
The SPFH complex HflK-HflC regulates aerobic respiration in bacteria
2025-04-07

The bacterial HflK-HflC membrane complex is a member of the highly conserved family of SPFH proteins, which are present in all domains of life and include eukaryotic stomatins, flotillins, and prohibitins. These proteins organize cell membranes and are involved in various processes. However, the exact physiological functions of most bacterial SPFH proteins remain unclear. Here, we report that the HflK-HflC complex in Escherichia coli is required for growth under high aeration. The absence of this complex causes a growth defect at high oxygen levels due to a reduced abundance of IspG, an essential iron-sulfur cluster enzyme in the isoprenoid biosynthetic pathway. This reduction might be related to lower stability of IspG and several other proteins, including the iron siderophore transporter TonB, in the absence of the HflK-HflC complex. Our results suggest that decreased IspG activity leads to lower levels of ubiquinone and misregulated expression of multiple respiratory enzymes, including cytochrome oxidases, and consequently reduced respiration and lower ATP levels. This impact of the hflK hflC deletion on aerobic respiration resembles the mitochondrial respiratory defects caused by the inactivation of prohibitins in mammalian and yeast cells, indicating functional parallels between these bacterial and eukaryotic SPFH proteins.
Case Report: FGFR2 inhibitor resistance via PIK3CA and CDKN2A/B in an intrahepatic cholangiocarcinoma patient with FGFR2-SH3GLB1 fusion
2025-04-07

FGFR2 fusions occur in up to 14% of patients with intrahepatic cholangiocarcinoma (iCCA) and have been considered as therapeutic target for FGFR inhibitors (FGFRi). However, response to targeted treatment may be limited due to the emergence of various resistance mechanisms. We report a case of recurrent iCCA in a 43-year-old patient with a FGFR2 fusion, who was treated with Lenvatinib. Next-generation sequencing (NGS) of tumor-normal DNA and tumor RNA under Lenvatinib treatment confirmed the FGFR2 fusion, however no further molecular resistance mutation was observed. After failure of FGFRi treatment (Lenvatinib and Infigratinib) ten months later, repeated NGS analysis revealed a new gain-of-function mutation in PIK3CA and a homozygous deletion of CDKN2A/B , potentially representing an acquired resistance mechanism. The emerging acquired resistance to FGFR inhibitor treatment has implications for subsequent treatment strategies.
Development of arithmetic across the lifespan: A registered report.
2025-04-07

Arithmetic skills are needed at any age. In everyday life, children to older adults calculate and deal with numbers. The processes underlying arithmetic seem to change with age. From childhood to younger adulthood, children get better in domain-specific numerical skills such as place-value processing. From younger to older adulthood, domain-general cognitive skills such as working memory decline. These skills are needed for complex arithmetic such as addition with carrying and subtraction with borrowing. This study investigates how the domain-specific (number magnitude, place-value processing) and domain-general (working memory, processing speed, inhibition) processes of arithmetic change across the lifespan. Thereby, arithmetic effects (carry and borrow effects), numerical effects (distance and compatibility effects), and cognitive skills were assessed in children, younger and older adolescents, and younger, middle-aged and older adults. The results showed that numerical and arithmetic skills improve from childhood to young adulthood and remain relatively stable throughout adulthood, even though domain-general processes, particularly working memory and processing speed, decline with age. While number magnitude and place-value processing both develop until adulthood, number magnitude processing shows deficits during aging, whereas place-value processing remains intact even in old age. The carry effect shifts from a categorical all-or-none decision (whether or not a carry operation is needed) to a more continuous magnitude process in adulthood, reflecting increasing reliance on domain-specific skills. In contrast, the borrow effect remains largely categorical across all age groups, depending on general cognitive processes. These results provide critical insights into how arithmetic skills change over the lifespan, relying on both domain-specific and domain-general processes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
The Hexamethylenetetramine Adduct [Mg3(H2O)14][Fe(CN)6]2(C6H12N4)4(H2O)4.18, Its Potential as Testing Agent for Mg2+ Ions, and the Formation of Ferromagnetic Fe3C
2025-04-07

Isotypic compounds [Mg 3 (H 2 O) 14 ][M(CN) 6 ] 2 ·4HMT· x H 2 O (HMT = hexamethylenetetramine or urotropine) with M = Fe, Cr, and Co are crystallized from aqueous solutions. The iron compound (M = Fe) is most remarkable because it crystallizes with distinctive thin, deep‐yellow crystal plates. The crystal structure of [Mg 3 (H 2 O) 14 ][Fe(CN) 6 ] 2 (C 6 H 12 N 4 ) 4 (H 2 O) 4.18 is solved and refined by X‐Ray single‐crystal diffraction, revealing the tetragonal space group P 4 c 2, with a = 14.8156(5) Å, and c = 32.890(3) Å (Z = 4). The structure contains finite cyanido‐bridged linear sequences of the type [(H 2 O) 5 Mg–(Fe(CN) 6 )–(Mg(H 2 O) 4 )–(Fe(CN) 6 )–Mg(H 2 O) 5 ] being arranged parallel to the tetragonal axis with HMT and crystal water molecules in‐between these patterns. The straightforward synthesis and the characteristic appearance of crystals of this compound can make this reaction a useful test to proof the presence of Mg 2+ ions in aqueous solution. Thermoanalytical studies, designed to investigate the loss of water molecules and the decomposition pathway, reveal this compound as a useful precursor for the preparation of ferromagnetic cementite (Fe 3 C).
PPDPF is not a key regulator of human pancreas development
2025-04-07

Given their capability to differentiate into each cell type of the human body, human pluripotent stem cells (hPSCs) provide a unique platform for developmental studies. In the current study, we employed this cell system to understand the role of pancreatic progenitor differentiation and proliferation factor (PPDPF), a protein that has been little explored so far. While the zebrafish orthologue exdpf is essential for exocrine pancreas specification, its importance for mammalian and human development has not been studied yet. We implemented a four times CRISPR/Cas9 nicking approach to knockout PPDPF in human embryonic stem cells (hESCs) and differentiated PPDPF KO/KO and PPDPF WT/WT cells towards the pancreatic lineage. In contrast to data obtained from zebrafish, a very modest effect of the knockout was observed in the development of pancreatic progenitors in vitro , not affecting lineage specification upon orthotopic transplantation in vivo . The modest effect is in line with the finding that genetic variants near PPDPF are associated with random glucose levels in humans, but not with type 2 diabetes risk, supporting that dysregulation of this gene may only result in minor alterations of glycaemic balance in humans. In addition, PPDPF is less organ- and cell type specifically expressed in higher vertebrates and its so far reported functions appear highly context-dependent.
Reading Orosius in eleventh-century Moissac: text and annotation in Paris BnF lat. 4871
2025-04-07

Abstract The text of Orosius’s Historiae preserved in Paris BnF lat. 4871 was copied at the southern French abbey of Moissac in the mid-eleventh century. This article uses this understudied manuscript to explore the roles Orosius could play in the intellectual life of a medieval monastic community. In particular, it focuses on the abundance of glosses and a distinctive prologue (the so-called Praefatiuncula in Orosio) that were copied as part of the Historiae and which shaped how readers at Moissac engaged with the text. A close examination of these paratexts reveals previously unnoticed connections between Moissac and northern French and especially Breton centres of learning. Moreover, the paratexts point towards a particular context of use, namely grammatical instruction. Taken together, these aspects provide new texture and historical depth to the long-held assumption that Orosius was regarded as a canonical source in the medieval period.
Pregnant Women’s Knowledge of Pelvic Floor and Related Dysfunctions: A Scoping Review
2025-04-08

Pregnancy and childbirth can have far-reaching effects on women’s pelvic floor health. It is important to educate pregnant women about pelvic floor health and potential birth-related pelvic floor (PF) changes as part of continuous midwifery care. This scoping review aims to identify the current state of research on knowledge and knowledge gaps in pregnant women regarding the PF and PF dysfunction (PFD) in order to derive conclusions and recommendations for midwifery care and midwifery science. This review follows the Arksey and O’Malley framework and the PRISMA Statement. The literature search was conducted on databases PubMed, CINAHL, and Web of Science using various search terms and defined inclusion criteria. Eleven articles were included. The results show a considerable context-related knowledge deficit among pregnant women, with a high prevalence of PFDs such as urinary incontinence (UI), fecal incontinence (FI), or prolapse symptoms (POP). All contributions emphasize the importance of improved specific education and health advice regarding the PF and PFD for pregnant women to close knowledge gaps and promote sustainable PF health. Demands are made on the professional group ‘midwife’, which emphasize the importance of specific and target group-appropriate educational concepts on the subject of the PF and PFD.
Foundation model of neural activity predicts response to new stimulus types
2025-04-09

Abstract The complexity of neural circuits makes it challenging to decipher the brain’s algorithms of intelligence. Recent breakthroughs in deep learning have produced models that accurately simulate brain activity, enhancing our understanding of the brain’s computational objectives and neural coding. However, it is difficult for such models to generalize beyond their training distribution, limiting their utility. The emergence of foundation models 1 trained on vast datasets has introduced a new artificial intelligence paradigm with remarkable generalization capabilities. Here we collected large amounts of neural activity from visual cortices of multiple mice and trained a foundation model to accurately predict neuronal responses to arbitrary natural videos. This model generalized to new mice with minimal training and successfully predicted responses across various new stimulus domains, such as coherent motion and noise patterns. Beyond neural response prediction, the model also accurately predicted anatomical cell types, dendritic features and neuronal connectivity within the MICrONS functional connectomics dataset 2 . Our work is a crucial step towards building foundation models of the brain. As neuroscience accumulates larger, multimodal datasets, foundation models will reveal statistical regularities, enable rapid adaptation to new tasks and accelerate research.