bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic anticancer therapy for urothelial carcinoma: UK oncologists’ perspective
Authors: Jones Robert J. , Crabb Simon J. , Linch Mark , Birtle Alison J. , McGrane John , Enting Deborah , Stevenson Robert , Liu Kin , Kularatne Bihani , Hussain Syed A. 
Published: January 2024

AbstractUrothelial carcinoma (UC) is a common cancer associated with a poor prognosis in patients with advanced disease. Platinum-based chemotherapy has remained the cornerstone of systemic anticancer treatment for many years, and recent developments in the treatment landscape have improved outcomes. In this review, we provide an overview of systemic treatment for UC, including clinical data supporting the current standard of care at each point in the treatment pathway and author interpretations from a UK perspective. Neoadjuvant cisplatin-based chemotherapy is recommended for eligible patients with muscle-invasive bladder cancer and is preferable to adjuvant treatment. For first-line treatment of advanced UC, platinum-eligible patients should receive cisplatin- or carboplatin-based chemotherapy, followed by avelumab maintenance in those without disease progression. Among patients unable to receive platinum-based chemotherapy, immune checkpoint inhibitor (ICI) treatment is an option for those with programmed death ligand 1 (PD-L1)–positive tumours. Second-line or later treatment options depend on prior treatment, and enfortumab vedotin is preferred after prior ICI and chemotherapy, although availability varies between countries. Additional options include rechallenge with platinum-based chemotherapy, an ICI, or non–platinum-based chemotherapy. Areas of uncertainty include the optimal number of first-line chemotherapy cycles for advanced UC and the value of PD-L1 testing for UC.
CAPG is a novel biomarker for early gastric cancer and is involved in the Wnt/β-catenin signaling pathway
Authors: Long Yan , Wu JiaQi , Shen Yu , Gan Chenxiao , Zhang Chuandong , Wang Gang , Jing Jiyong , Zhang Chenjing , Pan Wensheng 
Published: January 2024

AbstractPast studies have shown that the Gelsolin-like actin-capping protein (CAPG) regulates cell migration and proliferation and is strongly associated with tumor progression. We present the first study of the mechanism of action of CAPG in early gastric cancer (EGC). We demonstrate that CAPG expression is upregulated in gastric cancer (GC) especially EGC. CAPG promotes GC proliferation, migration, invasion, and metastasis in vivo and in vitro. More importantly, CAPG plays a role in GC by involving the Wnt/β-catenin signaling pathway. Our findings suggest that CAPG may function as a novel biomarker for EGC.
Unusual Sabatier principle on high entropy alloy catalysts for hydrogen evolution reactions
Authors: Chen Zhi Wen , Li Jian , Ou Pengfei , Huang Jianan Erick , Wen Zi , Chen LiXin , Yao Xue , Cai GuangMing , Yang Chun Cheng , Singh Chandra Veer , Jiang Qing 
Published: January 2024

AbstractThe Sabatier principle is widely explored in heterogeneous catalysis, graphically depicted in volcano plots. The most desirable activity is located at the peak of the volcano, and further advances in activity past this optimum are possible by designing a catalyst that circumvents the limitation entailed by the Sabatier principle. Herein, by density functional theory calculations, we discovered an unusual Sabatier principle on high entropy alloy (HEA) surface, distinguishing the “just right” (ΔGH* = 0 eV) in the Sabatier principle of hydrogen evolution reaction (HER). A new descriptor was proposed to design HEA catalysts for HER. As a proof-of-concept, the synthesized PtFeCoNiCu HEA catalyst endows a high catalytic performance for HER with an overpotential of 10.8 mV at −10 mA cm−2and 4.6 times higher intrinsic activity over the state-of-the-art Pt/C. Moreover, the unusual Sabatier principle on HEA catalysts can be extended to other catalytic reactions.
Gene-SGAN: discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering
Authors: Yang Zhijian , Wen Junhao , Abdulkadir Ahmed , Cui Yuhan , Erus Guray , Mamourian Elizabeth , Melhem Randa , Srinivasan Dhivya , Govindarajan Sindhuja T. , Chen Jiong , Habes Mohamad , Masters Colin L. , Maruff Paul , Fripp Jurgen , Ferrucci Luigi , Albert Marilyn S. , Johnson Sterling C. , Morris John C. , LaMontagne Pamela , Marcus Daniel S. , Benzinger Tammie L. S. , Wolk David A. , Shen Li , Bao Jingxuan , Resnick Susan M. , Shou Haochang , Nasrallah Ilya M. , Davatzikos Christos 
Published: January 2024

AbstractDisease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN – a multi-view, weakly-supervised deep clustering method – which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer’s disease and brain endophenotypes associated with hypertension, from MRI and single nucleotide polymorphism data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-associated neuroimaging phenotypes.
Conformational coupling of the sialic acid TRAP transporter HiSiaQM with its substrate binding protein HiSiaP
Authors: Peter Martin F. , Ruland Jan A. , Kim Yeojin , Hendricks Philipp , Schneberger Niels , Siebrasse Jan Peter , Thomas Gavin H. , Kubitscheck Ulrich , Hagelueken Gregor 
Published: January 2024

AbstractThe tripartite ATP-independent periplasmic (TRAP) transporters use an extra cytoplasmic substrate binding protein (SBP) to transport a wide variety of substrates in bacteria and archaea. The SBP can adopt an open- or closed state depending on the presence of substrate. The two transmembrane domains of TRAP transporters form a monomeric elevator whose function is strictly dependent on the presence of a sodium ion gradient. Insights from experimental structures, structural predictions and molecular modeling have suggested a conformational coupling between the membrane elevator and the substrate binding protein. Here, we use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from Haemophilus influenzae in different conformational states. The SBP, HiSiaP, is locked in its substrate-bound form and the transmembrane elevator, HiSiaQM, is locked in either its assumed inward- or outward-facing states. We characterize the disulfide-locked constructs and use single-molecule total internal reflection fluorescence (TIRF) microscopy to study their interactions. Our experiments demonstrate that the SBP and the transmembrane elevator are indeed conformationally coupled, meaning that the open and closed state of the SBP recognize specific conformational states of the transporter and vice versa.
Enabling nonconjugated polyesters emit full-spectrum fluorescence from blue to near-infrared
Authors: Chu Bo , Liu Xiong , Xiong Zuping , Zhang Ziteng , Liu Bin , Zhang Chengjian , Sun Jing Zhi , Yang Qing , Zhang Haoke , Tang Ben Zhong , Zhang Xing-Hong 
Published: January 2024

AbstractNear-infrared luminophores have many advantages in advanced applications, especially for structures without π-conjugation aromatic rings. However, the fabrication of red clusteroluminogens from nonconjugated polymers is still a big challenge, let alone the near-infrared clusteroluminogens. Here, we develop nonconjugated luminophores with full-spectrum from blue to near-infrared light (470 ~ 780 nm), based on color phenomenon of nonconjugated polyesters synthesized from the amine-initiated copolymerization of epoxides and cyclic anhydrides. We reveal that amines act as initiators attached to polymer chain ends. The formation of various amine-ester complexes in polyesters induces red to near-infrared light, conceptually, amine-ester complexed clusteroluminescence via intra/inter-chain charge transfer. Significantly, emission colors can be easily tuned by the contents and types of amines, microstructures of polyesters, and their concentration. This work provides a low-cost, scalable platform and strategy for the production of high-efficiency, multicolor luminescent materials.
PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity
Authors: Jayakumar Sundarraj , Patel Manthan , Boulet Fanny , Aziz Hadicha , Brooke Greg N. , Tummala Hemanth , Pradeepa Madapura M. 
Published: January 2024

AbstractR-loops that accumulate at transcription sites pose a persistent threat to genome integrity. PSIP1 is a chromatin protein associated with transcriptional elongation complex, possesses histone chaperone activity, and is implicated in recruiting RNA processing and DNA repair factors to transcription sites. Here, we show that PSIP1 interacts with R-loops and other proteins involved in R-loop homeostasis, including PARP1. Genome-wide mapping of PSIP1, R-loops and γ-H2AX in PSIP1-depleted human and mouse cell lines revealed an accumulation of R-loops and DNA damage at gene promoters in the absence of PSIP1. R-loop accumulation causes local transcriptional arrest and transcription-replication conflict, leading to DNA damage. PSIP1 depletion increases 53BP1 foci and reduces RAD51 foci, suggesting altered DNA repair choice. Furthermore, PSIP1 depletion increases the sensitivity of cancer cells to PARP1 inhibitors and DNA-damaging agents that induce R-loop-induced DNA damage. These findings provide insights into the mechanism through which PSIP1 maintains genome integrity at the site of transcription.
Multi-scale structures of the mammalian radial spoke and divergence of axonemal complexes in ependymal cilia
Authors: Meng Xueming , Xu Cong , Li Jiawei , Qiu Benhua , Luo Jiajun , Hong Qin , Tong Yujie , Fang Chuyu , Feng Yanyan , Ma Rui , Shi Xiangyi , Lin Cheng , Pan Chen , Zhu Xueliang , Yan Xiumin , Cong Yao 
Published: January 2024

AbstractRadial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. Atomic-resolution structures of metazoan RS and structures of axonemal complexes in ependymal cilia, whose rhythmic beating drives the circulation of cerebrospinal fluid, however, remain obscure. Here, we present near-atomic resolution cryo-EM structures of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic flexibility of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the cryo-ET and sub-tomogram averaging map of mouse ependymal cilia and build the models for RS1-3, IDAs, and N-DRC. Contrary to the conserved RS structure, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of Tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella, further exemplifying the structural diversity of mammalian motile cilia. Our findings shed light on the stepwise mammalian RS assembly mechanism, the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understanding on the etiology of ciliary dyskinesia-related ciliopathies and on the ependymal cilia in the development of hydrocephalus.
hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS)
Authors: Salapa Hannah E. , Thibault Patricia A. , Libner Cole D. , Ding Yulian , Clarke Joseph-Patrick W. E. , Denomy Connor , Hutchinson Catherine , Abidullah Hashim M. , Austin Hammond S. , Pastushok Landon , Vizeacoumar Frederick S. , Levin Michael C. 
Published: January 2024

AbstractNeurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results in differential of binding to RNA targets causing alternative RNA splicing, which contributes to neurodegeneration in MS and its models. Using RNAseq of MS brains, we discovered differential expression and aberrant splicing of hnRNP A1 target RNAs involved in neuronal function and RNA homeostasis. We confirmed this in vivo in experimental autoimmune encephalomyelitis employing CLIPseq specific for hnRNP A1, where hnRNP A1 differentially binds and regulates RNA, including aberrantly spliced targets identified in human samples. Additionally, dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical changes in splicing, corroborating hnRNP A1 dysfunction as a cause of neurodegeneration. Collectively, these data indicate hnRNP A1 dysfunction causes altered neuronal RNA splicing, resulting in neurodegeneration in MS.
Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC
Authors: Panja Sukanya , Truica Mihai Ioan , Yu Christina Y. , Saggurthi Vamshi , Craige Michael W. , Whitehead Katie , Tuiche Mayra V. , Al-Saadi Aymen , Vyas Riddhi , Ganesan Shridar , Gohel Suril , Coffman Frederick , Parrott James S. , Quan Songhua , Jha Shantenu , Kim Isaac , Schaeffer Edward , Kothari Vishal , Abdulkadir Sarki A. , Mitrofanova Antonina 
Published: January 2024

AbstractHeterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment.
Altered quorum sensing and physiology of Staphylococcus aureus during spaceflight detected by multi-omics data analysis
Authors: Hauserman Matthew R. , Ferraro Mariola J. , Carroll Ronan K. , Rice Kelly C. 
Published: January 2024

AbstractStaphylococcus aureus colonizes the nares of approximately 30% of humans, a risk factor for opportunistic infections. To gain insight into S. aureus virulence potential in the spaceflight environment, we analyzed RNA-Seq, cellular proteomics, and metabolomics data from the “Biological Research in Canisters-23” (BRIC-23) GeneLab spaceflight experiment, a mission designed to measure the response of S. aureus to growth in low earth orbit on the international space station. This experiment used Biological Research in Canisters-Petri Dish Fixation Units (BRIC-PDFUs) to grow asynchronous ground control and spaceflight cultures of S. aureus for 48 h. RNAIII, the effector of the Accessory Gene Regulator (Agr) quorum sensing system, was the most highly upregulated gene transcript in spaceflight relative to ground controls. The agr operon gene transcripts were also highly upregulated during spaceflight, followed by genes encoding phenol-soluble modulins and secreted proteases, which are positively regulated by Agr. Upregulated spaceflight genes/proteins also had functions related to urease activity, type VII-like Ess secretion, and copper transport. We also performed secretome analysis of BRIC-23 culture supernatants, which revealed that spaceflight samples had increased abundance of secreted virulence factors, including Agr-regulated proteases (SspA, SspB), staphylococcal nuclease (Nuc), and EsxA (secreted by the Ess system). These data also indicated that S. aureus metabolism is altered in spaceflight conditions relative to the ground controls. Collectively, these data suggest that S. aureus experiences increased quorum sensing and altered expression of virulence factors in response to the spaceflight environment that may impact its pathogenic potential.
A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells
Authors: Naaldijk Yahaira , Fernández Belén , Fasiczka Rachel , Fdez Elena , Leghay Coline , Croitoru Ioana , Kwok John B. , Boulesnane Yanisse , Vizeneux Amelie , Mutez Eugenie , Calvez Camille , Destée Alain , Taymans Jean-Marc , Aragon Ana Vinagre , Yarza Alberto Bergareche , Padmanabhan Shalini , Delgado Mario , Alcalay Roy N. , Chatterton Zac , Dzamko Nicolas , Halliday Glenda , Ruiz-Martínez Javier , Chartier-Harlin Marie-Christine , Hilfiker Sabine 
Published: January 2024

AbstractParkinson´s disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for disease intervention. However, the ability to stratify patients who will benefit from such treatment modalities based on shared etiology is critical for the success of disease-modifying therapies. Ciliary and centrosomal alterations are commonly associated with pathogenic LRRK2 kinase activity and can be detected in many cell types. We previously found centrosomal deficits in immortalized lymphocytes from G2019S-LRRK2 PD patients. Here, to investigate whether such deficits may serve as a potential blood biomarker for PD which is susceptible to LRKK2 inhibitor treatment, we characterized patient-derived cells from distinct PD cohorts. We report centrosomal alterations in peripheral cells from a subset of early-stage idiopathic PD patients which is mitigated by LRRK2 kinase inhibition, supporting a role for aberrant LRRK2 activity in idiopathic PD. Centrosomal defects are detected in R1441G-LRRK2 and G2019S-LRRK2 PD patients and in non-manifesting LRRK2 mutation carriers, indicating that they accumulate prior to a clinical PD diagnosis. They are present in immortalized cells as well as in primary lymphocytes from peripheral blood. These findings indicate that analysis of centrosomal defects as a blood-based patient stratification biomarker may help nominate idiopathic PD patients who will benefit from LRRK2-related therapeutics.
Selective gene expression maintains human tRNA anticodon pools during differentiation
Authors: Gao Lexi , Behrens Andrew , Rodschinka Geraldine , Forcelloni Sergio , Wani Sascha , Strasser Katrin , Nedialkova Danny D. 
Published: January 2024

AbstractTransfer RNAs are essential for translating genetic information into proteins. The human genome contains hundreds of predicted tRNA genes, many in multiple copies. How their expression is regulated to control tRNA repertoires is unknown. Here we combined quantitative tRNA profiling and chromatin immunoprecipitation with sequencing to measure tRNA expression following the differentiation of human induced pluripotent stem cells into neuronal and cardiac cells. We find that tRNA transcript levels vary substantially, whereas tRNA anticodon pools, which govern decoding rates, are more stable among cell types. Mechanistically, RNA polymerase III transcribes a wide range of tRNA genes in human induced pluripotent stem cells but on differentiation becomes constrained to a subset we define as housekeeping tRNAs. This shift is mediated by decreased mTORC1 signalling, which activates the RNA polymerase III repressor MAF1. Our data explain how tRNA anticodon pools are buffered to maintain decoding speed across cell types and reveal that mTORC1 drives selective tRNA expression during differentiation.
Measuring the presence and incidence of cholera in Hindustan: New data from primary sources for the colonial era
Authors: Aslam Maqsood , Baudin Thomas , Farvaque Etienne , Marakbi Reda 
Published: January 2024

AbstractWe build a new dataset covering 90 years of Cholera spreading in Hindustan from 1814 to 1904. We gather data from a collection of primary sources issued from medical reports. We propose a harmonization procedure to make these data comparable and corresponding to the current borders of India, Pakistan, Nepal, and Bangladesh. Our methodology is corroborated when comparing our newly produced data with other accounts, in particular Roger (1926)’s estimations. It opens the door to research aiming at estimating the effect of the successive waves of Cholera on the economic, social and epidemiological dynamics of the region.
ePyDGGA: automatic configuration for fitting epidemic curves
Authors: Alòs Josep , Ansótegui Carlos , Dotu Ivan , García-Herranz Manuel , Pastells Pol , Torres Eduard 
Published: January 2024

AbstractMany epidemiological models and algorithms are used to fit the parameters of a given epidemic curve. On many occasions, fitting algorithms are interleaved with the actual epidemic models, which yields combinations of model-parameters that are hard to compare among themselves. Here, we provide a model-agnostic framework for epidemic parameter fitting that can (fairly) compare different epidemic models without jeopardizing the quality of the fitted parameters. Briefly, we have developed a Python framework that expects a Python function (epidemic model) and epidemic data and performs parameter fitting using automatic configuration. Our framework is capable of fitting parameters for any type of epidemic model, as long as it is provided as a Python function (or even in a different programming language). Moreover, we provide the code for different types of models, as well as the implementation of 4 concrete models with data to fit them. Documentation, code and examples can be found at https://ulog.udl.cat/static/doc/epidemic-gga/html/index.html.
Verification labels for rovibronic quantum-state energy uncertainties
Authors: Árendás Péter , Furtenbacher Tibor , Császár Attila G. 
Published: January 2024

AbstractTransition wavenumbers contained in line-by-line rovibronic databases can be compromised by errors of various nature. When left undetected, these errors may result in incorrect quantum-state energies, potentially compromising a large number of derived spectroscopic data. Spectroscopic networks treat the complete set of line-by-line spectroscopic data as a large graph, and through a least-squares refinement the measured line positions are converted into empirical quantum-state energies. Spectroscopic networks also offer a highly useful framework to develop mathematical tools helping to identify possible errors and conflicts within the dataset. For example, wavenumber errors can be detected by checking for violations of the law of energy conservation. This paper describes a new graph-theory tool, which results in so-called verification labels for the quantum states. Verification labels help to express the vulnerability of a calculated empirical energy value and its uncertainty against possible wavenumber errors, providing complementary information to simple statistical uncertainties.