bluuebunny/crossref_metadata_2025_split huggingface dataset:
NT-proBNP detection with a one-step magnetic lateral flow channel assay
Authors: Strohmaier-Nguyen Dan , Horn Carina , Baeumner Antje J. 
Published: March 2024

AbstractPoint-of-care sensors targeting blood marker analysis must be designed to function with very small volumes since acquiring a blood sample through a simple, mostly pain-free finger prick dramatically limits the sample size and comforts the patient. Therefore, we explored the potential of converting a conventional lateral flow assay (LFA) for a significant biomarker into a self-contained and compact polymer channel-based LFA to minimize the sample volume while maintaining the analytical merits. Our primary objective was to eliminate the use of sample-absorbing fleece and membrane materials commonly present in LFAs. Simultaneously, we concentrated on developing a ready-to-deploy one-step LFA format, characterized by dried reagents, facilitating automation and precise sample transport through a pump control system. We targeted the detection of the heart failure biomarker NT-proBNP in only 15 µL human whole blood and therefore implemented strategies that ensure highly sensitive detection. The biosensor combines streptavidin-functionalized magnetic beads (MNPs) as a 3D detection zone and fluorescence nanoparticles as signal labels in a sandwich-based immunoassay. Compared to the currently commercialized LFA, our biosensor demonstrates comparable analytical performance with only a tenth of the sample volume. With a detection limit of 43.1 pg∙mL−1 and a mean error of 18% (n ≥ 3), the biosensor offers high sensitivity and accuracy. The integration of all-dried long-term stable reagents further enhances the convenience and stability of the biosensor. This lateral flow channel platform represents a promising advancement in point-of-care diagnostics for heart failure biomarkers, offering a user-friendly and sensitive platform for rapid and reliable testing with low finger-prick blood sample volumes.
Graphical abstract
Motor learning and performance in schizophrenia and aging: two different patterns of decline
Authors: Hulstijn Wouter , Cornelis Claudia , Morsel Anne , Timmers Maarten , Morrens Manuel , Sabbe Bernard G. C. 
Published: March 2024

AbstractPsychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.
Rituximab, gemcitabine and oxaliplatin in relapsed or refractory indolent and mantle cell lymphoma: results of a multicenter phase I/II-study of the German Low Grade Lymphoma Study Group
Authors: Scheubeck Gabriel , Hoffmann Martin , Jurinovic Vindi , Fischer Luca , Unterhalt Michael , Schmidt Christian , Böck Hans-Peter , Dührsen Ulrich , Kaesberger Joachim , Kremers Stephan , Lindemann Hans-Walter , Mantovani Luisa , Hiddemann Wolfgang , Hoster Eva , Dreyling Martin ,   on behalf of the German Lymphoma Alliance (GLA)
Published: March 2024

AbstractRituximab, gemcitabine and oxaliplatin (R-GemOx) has demonstrated to be effective and safe in lymphoma patients. We aimed to determine the maximum tolerated dose (MTD) of oxaliplatin in combination with rituximab and gemcitabine and to explore the efficacy and safety of R-GemOx in relapsed or refractory (r/r) indolent and mantle cell lymphoma (MCL). In this single-arm, phase I/II trial, we enrolled 55 patients with r/r indolent lymphoma and MCL not suitable for autologous stem-cell transplantation. Patients received 4 cycles of R-GemOx. In the dose escalation group, 70 mg/m2 of oxaliplatin was applied and interindividually increased by 10 mg/m2 until the MTD was reached together with fixed doses of rituximab and gemcitabine. At the oxaliplatin MTD, an extension cohort was opened. Primary aim was to detect an overall response rate (ORR) greater than 65% (α = 0.05). Oxaliplatin 70 mg/m2 (MTD) was chosen for the extension cohort after 3 of 6 patients experienced a DLT at 80 mg/m2. Among 46 patients evaluable for the efficacy analysis ORR was 72% (33/46), missing the primary aim of the study (p = 0.21). After a median follow-up of 7.9 years, median PFS and OS were 1.0 and 2.1 years. Most frequent grade ≥ 3 adverse events were cytopenias. R-GemOx induces decent response rates in r/r indolent lymphoma and MCL, though novel targeted therapies have largely replaced chemotherapy in the relapse setting. Particularly in MCL, R-GemOx might be an alternative option in late relapses or as bridging to CAR-T-cells. This study was registered with ClinicalTrials.gov on Aug 4th, 2009, number NCT00954005.
Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer
Authors: Lee Elaine Yuen Phin , Ip Philip Pun Ching , Tse Ka Yu , Chiu Keith Wan Hang , Chu Mandy Man Yee , Chai Yu Ka , Wu Philip Yuguang , Law Jessica Yun Pui , Kwok Shuk Tak , Chiu Wan Kam , Ngan Hextan Yuen Sheung 
Published: March 2024

Abstract
Objectives
The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC).

Materials and methods
This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III–IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar’s test.

Results
In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05).

Conclusion
2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC.

Clinical relevance statement
2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery.

Key Points
• Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy.
• 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT.
• Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.
Overbidding and underbidding in package allocation problems
Authors: Núñez Marina , Robles Francisco 
Published: March 2024

AbstractWe study the problem of allocating packages of different objects to a group of bidders. A rule is overbidding-proof if no bidder has incentives to bid above his actual valuations. We prove that if an efficient rule is overbidding-proof, then each winning bidder pays a price between his winning bid and what he would pay in a Vickrey auction for the same package. In counterpart, the set of rules that satisfy underbidding-proofness always charge a price below the corresponding Vickrey price. A new characterization of the Vickrey allocation rule is provided with a weak form of strategy-proofness. The Vickrey rule is the only rule that satisfies efficiency, individual rationality, overbidding-proofness and underbidding-proofness. Our results are also valid on the domains of monotonic valuations and of single-minded bidders. Finally a family of overbidding rules is introduced that price the assigned packages at a fixed average of the Vickrey price and the pay-as-bid price.
Insights into taxadiene synthase catalysis and promiscuity facilitated by mutability landscape and molecular dynamics
Authors: He Siqi , Abdallah Ingy I. , van Merkerk Ronald , Quax Wim J. 
Published: March 2024

Abstract
Main conclusion
Protein modeling, carbocation docking, and molecular dynamics along with structure-based mutability landscapes provided insight into taxadiene synthase catalysis (first step of the anticancer Taxol biosynthesis), protein structure–function correlations, and promiscuity.

Abstract
Plant terpenes belong to one of the largest and most diverse classes of natural products. This diversity is driven by the terpene synthase enzyme family which comprises numerous different synthases, several of which are promiscuous. Taxadiene synthase (TXS) is a class I diterpene synthase that catalyzes the first step in the biosynthesis pathway of the diterpene Taxol, an anticancer natural product produced by the Taxus plant. Exploring the molecular basis of TXS catalysis and its promiscuous potential garnered interest as a necessary means for understanding enzyme evolution and engineering possibilities to improve Taxol biosynthesis. A catalytically active closed conformation TXS model was designed using the artificial intelligence system, AlphaFold, accompanied by docking and molecular dynamics simulations. In addition, a mutability landscape of TXS including 14 residues was created to probe for structure–function relations. The mutability landscape revealed no mutants with improved catalytic activity compared to wild-type TXS. However, mutations of residues V584, Q609, V610, and Y688 showed high degree of promiscuity producing cembranoid-type and/or verticillene-type major products instead of taxanes. Mechanistic insights into V610F, V584M, Q609A, and Y688C mutants compared to the wild type revealed the trigger(s) for product profile change. Several mutants spanning residues V584, Q609, Y688, Y762, Q770, and F834 increased production of taxa-4(20),11(12)-diene which is a more favorable substrate for Taxol production compared to taxa-4(5),11(12)-diene. Finally, molecular dynamics simulations of the TXS reaction cascade revealed residues involved in ionization, carbocation stabilization, and cyclization ushering deeper understanding of the enzyme catalysis mechanism.

Graphical abstract
Transcriptome analysis reveals the clinical significance of CXCL13 in Pan-Gyn tumors
Authors: Ding Yue , Zhou Quan , Ding Bo , Zhang Yang , Shen Yang 
Published: March 2024

Abstract
Background
Gynecologic and breast tumors (Pan-Gyn) exhibit similar characteristics, and the role of CXCL13 in anti-tumor immunity and it’s potential as a biomarker for immune checkpoint blockade (ICB) therapy have been gradually revealed. However, the precise role of CXCL13 in Pan-Gyn remains unclear, lacking a systematic analysis.

Methods
We analyzed 2497 Pan-Gyn samples from the TCGA database, categorizing them into high and low CXCL13 expression groups. Validation was conducted using tumor expression datasets sourced from the GEO database. Correlation between CXCL13 and tumor immune microenvironment (TIME) was evaluated using multiple algorithms. Finally, we established nomograms for 3-year and 5-year mortality.

Results
High expression of CXCL13 in Pan-Gyn correlates with a favorable clinical prognosis, increased immune cell infiltration, and reduced intra-tumor heterogeneity. Model was assessed using the C-index [BRCA: 0.763 (0.732–0.794), UCEC: 0.821 (0.793–0.849), CESC: 0.736 (0.684–0.788), and OV: 0.728 (0.707–0.749)], showing decent prediction of discrimination and calibration.

Conclusion
Overall, this study provides comprehensive insights into the commonalities and differences of CXCL13 in Pan-Gyn, potentially opening new avenues for personalized treatment.
Trisomy silencing by XIST: translational prospects and challenges
Authors: Gupta Khusali , Czerminski Jan T. , Lawrence Jeanne B. 
Published: March 2024

AbstractXIST RNA is heavily studied for its role in fundamental epigenetics and X-chromosome inactivation; however, the translational potential of this singular RNA has been much less explored. This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility of XIST for chromosome dosage disorders, particularly Down syndrome (DS). Remarkably, it was shown in vitro that expression of an XIST transgene inserted into one chromosome 21 can comprehensively silence that chromosome and “dosage compensate” Trisomy 21, the cause of DS. Here we summarize recent findings and discuss potential paths whereby ability to induce “trisomy silencing” can advance translational research for new therapeutic strategies. Despite its common nature, the underlying biology for various aspects of DS, including cell types and pathways impacted (and when), is poorly understood. Recent studies show that an inducible iPSC system to dosage-correct chromosome 21 can provide a powerful approach to unravel the cells and pathways directly impacted, and the developmental timing, information key to design pharmacotherapeutics. In addition, we discuss prospects of a more far-reaching and challenging possibility that XIST itself could be developed into a therapeutic agent, for targeted cellular “chromosome therapy”. A few rare case studies of imbalanced X;autosome translocations indicate that natural XIST can rescue an otherwise lethal trisomy. The potential efficacy of XIST transgenes later in development faces substantial biological and technical challenges, although recent findings are encouraging, and technology is rapidly evolving. Hence, it is compelling to consider the transformative possibility that XIST-mediated chromosome therapy may ultimately be developed, for specific pathologies seen in DS, or other duplication disorders.
Sexuality, intimacy, and body image among adolescents and young adults with cancer: a qualitative, explorative study
Authors: Bentsen Line , Aagesen Maria , Bidstrup Pernille , Hjerming Maiken , Pappot Helle 
Published: March 2024

Abstract
Aim
The aim of this study was threefold: (1) to explore Danish adolescents and young adults’ (AYAs) thoughts concerning sexual health particularly focusing on sexuality, intimacy, and body image throughout a cancer trajectory, (2) to investigate how AYAs experience healthcare professionals address of- and respond to sexual health issues, and (3) to identify AYAs’ suggestions on how to support conversation about sexual health.

Methods
A qualitative, single-center study was conducted, including AYAs (18–29 years) diagnosed with cancer recruited at the University Hospital of Copenhagen, Rigshospitalet. Individual semi-structured interviews were conducted from January–February 2023, recorded, transcribed verbatim, and analyzed using thematic analysis.

Results
Twelve participants were interviewed, aged 20–29; five were diagnosed with hematological- and seven with oncological cancer. Our analyses yielded three themes: (1) sexuality and body image as part of the identity, (2) excluding relatives in conversations about sexual health, and (3) uncertainty how to discuss sexual health with healthcare professionals. Finally, the AYAs’ suggestions to support conversations about sexual health were organized into six thematic categories.

Conclusion
In this study, participants experienced altered sexual subsequent impacts on body image and self-esteem during their cancer trajectory. While some adapted to these changes, discussing them with healthcare providers was difficult, especially in the presence of relatives, as the AYAs wanted to shield them from additional concerns. To enhance support, AYAs suggest regular discussions on sexual health and the use of a dialog tool by healthcare professionals.
A note concerning some aspects for application of a thermodynamic extremal principle (TEP) for continua
Authors: Fischer F. D. , Zickler G. A. , Hackl K. , Svoboda J. 
Published: March 2024

AbstractA matter of fact is that extremal principles have been introduced in mechanics in more (Euler, Lagrange) or less (Hamilton) than 200 years ago. One may also observe an impact of thermodynamic extremal principles based on maximum dissipation due to all the entropy production expressed in several disciplines. According fields are theory of communication, statistical mechanics and later physics of earth since already 70 years. The current paper offers some (historical) overview on several applications. “Ziegler’s principle” is an implementation of the maximum entropy production going out to the dissipation and yielding a maximum dissipation. The goal of this paper is now the implementation of this extremal principle performed along an algebraic concept. Such a concept can be extended to a system with several internal variables as outlined by Coleman and Gurtin in context with the Gibbs (free) energy.
Prediction of matrilineal specific patatin-like protein governing in-vivo maternal haploid induction in maize using support vector machine and di-peptide composition
Authors: Dutta Suman , Zunjare Rajkumar U. , Sil Anirban , Mishra Dwijesh Chandra , Arora Alka , Gain Nisrita , Chand Gulab , Chhabra Rashmi , Muthusamy Vignesh , Hossain Firoz 
Published: March 2024

AbstractThe mutant matrilineal (mtl) gene encoding patatin-like phospholipase activity is involved in in-vivo maternal haploid induction in maize. Doubling of chromosomes in haploids by colchicine treatment leads to complete fixation of inbreds in just one generation compared to 6–7 generations of selfing. Thus, knowledge of patatin-like proteins in other crops assumes great significance for in-vivo haploid induction. So far, no online tool is available that can classify unknown proteins into patatin-like proteins. Here, we aimed to optimize a machine learning-based algorithm to predict the patatin-like phospholipase activity of unknown proteins. Four different kernels [radial basis function (RBF), sigmoid, polynomial, and linear] were used for building support vector machine (SVM) classifiers using six different sequence-based compositional features (AAC, DPC, GDPC, CTDC, CTDT, and GAAC). A total of 1170 protein sequences including both patatin-like (585 sequences) from various monocots, dicots, and microbes; and non-patatin-like proteins (585 sequences) from different subspecies of Zea mays were analyzed. RBF and polynomial kernels were quite promising in the prediction of patatin-like proteins. Among six sequence-based compositional features, di-peptide composition attained > 90% prediction accuracies using RBF and polynomial kernels. Using mutual information, most explaining dipeptides that contributed the highest to the prediction process were identified. The knowledge generated in this study can be utilized in other crops prior to the initiation of any experiment. The developed SVM model opened a new paradigm for scientists working in in-vivo haploid induction in commercial crops. This is the first report of machine learning of the identification of proteins with patatin-like activity.
Specific lineage transition of tumor-associated macrophages elicits immune evasion of ascitic tumor cells in gastric cancer with peritoneal metastasis
Authors: Li Yilin , Jiang Lei , Chen Yang , Li Yanyan , Yuan Jiajia , Lu Jialin , Zhang Zizhen , Liu Shengde , Feng Xujiao , Xiong Jiaxin , Jiang Yan , Zhang Xiaotian , Li Jian , Shen Lin 
Published: March 2024

Abstract
Background
Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs).

Methods
Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs.

Results
Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway.

Conclusions
For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.

Graphical Abstract
Schematic of the immune TME of ascites and the crosstalk with aDTCs in patients with PM-GC. In ascites with TAM-dominant TME, the ascitic TAMs undergo CTS-to-C1Q transition to support multiple phases of aDTC dissemination, including aDTC homing, proliferation, immune escape, and therapeutic resistance. While in ascites with T-cell-dominant TME, enriched T cells do not imply “immune-hot” TME. Infiltrated CD8+ T cells are GZMK+ precursor-exhausted cells that have lost their capacity to kill tumor cells. (Abbreviations: aDTC ascites-disseminated tumor cells, CTS cathepsin, TAM Tumor-associated macrophages, TME tumor microenvironment)