bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery
Authors: Dijkstra Esmée A. , Nilsson Per J. , Hospers Geke A.P. , Bahadoer Renu R. , Meershoek-Klein Kranenbarg Elma , Roodvoets Annet G.H. , Putter Hein , Berglund Åke , Cervantes Andrés , Crolla Rogier M.P.H. , Hendriks Mathijs P. , Capdevila Jaume , Edhemovic Ibrahim , Marijnen Corrie A.M. , van de Velde Cornelis J.H. , Glimelius Bengt , van Etten Boudewijn ,   Collaborative Investigators
Published: January 2023

Objective:
To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at 5 years.

Background:
Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At 3 years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial.

Methods:
A total of 920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional postoperative chemotherapy). LRFs, including early LRF (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed.

Results:
Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively (P=0.07), in which EXP patients were more often treated with 3-dimensional-conformed radiotherapy (P=0.029). In the EXP group, LRR was detected more often [44/431 (10%) vs. 26/428 (6%); P=0.027], with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P=0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were the significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable [hazard ratio: 0.76 (95% CI, 0.46–1.26); P=0.29].

Conclusions:
The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.
A workflow for incorporating cross-sectional data into the calibration of dynamic models
Authors: Fischer-Holzhausen Sophie , Röblitz Susanna 
Published: January 2023

AbstractMathematical modelling and dynamic simulations are commonly used in systems medicine to investigate the interactions between various biological entities in time. The level of model complexity is mainly restricted by the number of model parameters that can be estimated from available experimental data and prior knowledge. The calibration of dynamic models usually requires longitudinal data from multiple individuals, which is challenging to obtain and, consequently, not always available. On the contrary, the collection of cross-sectional data is often more feasible. Here, we demonstrate how the parameters of individual dynamic models can be estimated from such cross-sectional data using a Bayesian updating method. We illustrate this approach on a model for puberty in girls with cross-sectional hormone measurement data.
Species delimitation of eight ascidian (Tunicata) species from the North Eastern Mediterranean
Authors: Karahan Arzu , Temiz Berivan , Öztürk Esra , Douek Jacob , Rinkevich Baruch 
Published: January 2023

AbstractMembers of the tunicates, a subphylum of marine filter-feeder chordates, inhabit all marine and oceanic habitats from the subtidal to the abyssal. Considered as the closest relatives to the vertebrates, the tunicates are widely used as model organisms for evo-devo, allorecognition, senescence, and whole-body regeneration studies. Yet, species boundaries are poorly understood due to high morphological and genetic plasticity that characterize many tunicates taxa. Here we study taxonomy and the distribution of eight tunicate species (Botrylloides niger Herdman, 1886/ aff. leachii, Botrylloides israelienseBrunetti, 2009,Botrylloides sp., Botrylloides anceps(Herdman, 1891),Botryllus schlosseri(Pallas, 1766),Didemnum perlucidumMonniot F., 1983,Symplegma brakenhielmi(Michaelsen, 1904) andPolyclinum constellatumSavigny, 1816) sampled from six Turkish North Eastern Mediterranean Sea sites and employed the mitochondrial barcoding marker (COI) for evaluating the relationships among geographically restricted and widely spread ascidian species. Species delimitation analysis was conducted using NCBI and the present study sequences. Morphological examinations were first done in the field and then, styelide colonies were cultured in the laboratory and studied using stereo and light microscopes. A putative newBotrylloidesspecies (Botrylloides sp.) from the Antalya region was revealed, with 99% matching on the COI gene from Saudi Arabia, further awaiting for detailed traditional taxonomy.
Tipifarnib potentiates the antitumor effects of PI3Kα inhibition inPIK3CA- andHRAS-dysregulated HNSCC via convergent inhibition of mTOR activity
Authors: Smith Alison E. , Chan Stacia , Wang Zhiyong , McCloskey Asako , Reilly Quinn , Wang Jayden Z. , Patel Hetika Vora , Koshizuka Keiichi , Soifer Harris S. , Kessler Linda , Dayoub Ashley , Villaflor Victoria , Adkins Douglas , Bruce Justine , Ho Alan , Batista Cesar Perez , Hanna Glenn , Gascó Hernández Amaya , Saunders Andrew , Dale Stephen , Gutkind J. Silvio , Burrows Francis , Malik Shivani 
Published: January 2023

AbstractOutcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival ranging from 6 to 18 months. For those who progress on standard of care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. We find that tipifarnib synergizes with alpelisib at the level of mTOR in PI3Kα-or HRAS-dependent HNSCCs, leading to marked cytotoxicityin vitroand tumor regressionin vivo. Based on these findings, we have launched the KURRENT-HN trial to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy.SignificanceBacked by strong mechanistic rationale, the combination of alpelisib and tipifarnib has the potential to benefit >45% of R/M HNSCC patients. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, thereby enhancing their clinical utility.
Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential
Authors: Tan Cedric C.S. , Trew Jahcub , Peacock Thomas P. , Mok Kai Yi , Hart Charlie , Lau Kelvin , Ni Dongchun , Orme C. David L. , Ransome Emma , Pearse William D. , Coleman Christopher M. , Bailey Dalan , Thakur Nazia , Quantrill Jessica L. , Sukhova Ksenia , Richard Damien , Kahane Laura , Woodward Guy , Bell Thomas , Worledge Lisa , Nunez-Mino Joe , Barclay Wendy , van Dorp Lucy , Balloux Francois , Savolainen Vincent 
Published: January 2023

AbstractThere has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown and warrants closer surveillance.
Corticostriatal Responses to Social Reward are Linked to Trait Reward Sensitivity and Subclinical Substance Use in Young Adults
Authors: Wyngaarden James B. , Johnston Camille R. , Sazhin Daniel , Dennison Jeff B. , Zaff Ori , Fareri Dominic , McCloskey Michael , Alloy Lauren B. , Smith David V. , Jarcho Johanna M. 
Published: January 2023

AbstractAberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g., positive peer feedback). Testing this relation is critical for predicting risk for development of substance use disorder. In this pre-registered study, participants (N=44) underwent fMRI while completing well-matched tasks that assess neural response to reward in social and monetary domains. Contrary to our hypotheses, aberrant reward sensitivity blunted the relationship between substance use and striatal activation during receipt of rewards, regardless of domain. Moreover, exploratory whole-brain analyses showed unique relations between substance use and social rewards in temporoparietal junction. Psychophysiological interactions demonstrated that aberrant reward sensitivity is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Finally, we found that substance use was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of reward sensitivity. These findings demonstrate nuanced relations between reward sensitivity and substance use, even among those without substance use disorder, and suggest altered reward-related engagement of cortico-VS responses as potential predictors of developing disordered behavior.
Mzion enables deep and precise identification of peptides in data-dependent acquisition proteomics
Authors: Zhang Qiang 
Published: January 2023

AbstractSensitive and reliable identification of proteins and peptides pertains the basis of proteomics. We introduce Mzion, a new database search tool for data-dependent acquisition (DDA) proteomics. Our tool utilizes an intensity tally strategy and achieves generally a higher performance in terms of depth and precision across twenty datasets, ranging from large-scale to single-cell proteomics. Compared to several other search engines, Mzion matches on average 20% more peptide spectra at tryptic enzymatic specificity and 80% more at no enzymatic specificity from six large-scale, global datasets. Mzion also identifies more phosphopeptide spectra that can be explained by fewer proteins, demonstrated by six large-scale, local datasets corresponding to the global data. Our findings highlight the potential of Mzion for improving proteomic analysis and advancing our understanding of protein biology.
curatedPCaData: Integration of clinical, genomic, and signature features in a curated and harmonized prostate cancer data resource
Authors: Laajala Teemu D , Sreekanth Varsha , Soupir Alex , Creed Jordan , Calboli Federico CF , Singaravelu Kalaimathy , Orman Michael , Colin-Leitzinger Christelle , Gerke Travis , Fidley Brooke L. , Tyekucheva Svitlana , Costello James C 
Published: January 2023

ABSTRACTGenomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets. The full potential of such data is yet to be realized as independent datasets exist in different repositories, have been processed using different pipelines, and derived and clinical features are often not provided or unstandardized. Here, we present thecuratedPCaDataR package, a harmonized data resource representing >2900 primary tumor, >200 normal tissue, and >500 metastatic PCa samples across 19 datasets processed using standardized pipelines with updated gene annotations. We show that meta-analysis across harmonized studies has great potential for robust and clinically meaningful insights.curatedPCaDatais an open and accessible community resource with code made available for reproducibility.
Brain Oscillations during Visuomotor Processing in Children with ASD
Authors: Wilson Emily May , An Kyung-min 
Published: January 2023

AbstractAutism Spectrum disorder (ASD) has been reported to often involve significant motor dysfunction in addition to other core traits. While individual differences in visual processing have also been noted in individuals with ASD. However, the brain oscillations between visual and motor processing in ASD are poorly understood due to a lack of research surrounding the topic. To elucidate this, we focused on the power-power correlation between visual- and motor-related oscillations. We recorded magnetoencephalography in 18 children with ASD and 19 IQ-matched typically developing children aged 4-7 while they pressed a button during a visual-targeted motor task. We estimated visual- and motor-related brain oscillations and focused on the gamma oscillations. We observed gamma oscillatory power changes during the visual-targeted motor task in both groups. We further found statistically significant differences in motor-related gamma power in the right primary motor cortex, but not in the left primary motor cortex between the two groups. We finally found a significant correlation between the left visual gamma power (50-60 Hz, 150-450ms) and the left motor gamma power (70-90 Hz, 0-100 ms) in the TD group. The current findings revealed differences in visuomotor processing in individuals with ASD compared to TD children. These results may be helpful in understanding the neural mechanisms underlying visuomotor processing in ASD, supporting the development of a potential biomarker for ASD.
Optimal Cellular Phenotypic Adaptation in Fluctuating Environments
Authors: George Jason T. 
Published: January 2023

AbstractPhenotypic adaptation is a core design feature of bacterial populations and multicellular systems navigating highly variable environments. Recent empirical data implicates the role of memory-driven decision-making in cellular systems navigating uncertain future nutrient environments based on prior experience, wherein a distinct growth phenotype emerges in fluctuating conditions. We develop a simple stochastic mathematical model to describe the cellular decision-making required for systems to optimally navigate such uncertainty. We demonstrate that adaptive populations capable of sensing their environment and estimating the nutrient landscape more efficiently traverse changing environments. We find during environmental transitions that larger memory capacities strike a trade-off between inertia of past environmental memory and higher resolution for estimating the optimal phenotype whenever the underlying landscape is close to a critical break-even point. Moreover, systems that tune their memory capacity avoid growth penalties resulting from maladaptive phenotypes following changes to the metabolic landscape. Our model predicts that the nutrient availability of adaptive cells is universally reduced in fluctuating nutritional environments relative to those in constant ones, which recapitulates empirical observations in bacterial systems. Our findings demonstrate that this deviation is a consequence of environmental mis-estimation together with bet-hedging in uncertain adaptive landscapes, and suggests that this deviation is fully determined by cellular memory capacity and the proximity of the environmental landscape to the system’s critical break-even environment. We anticipate that our mathematical framework will be more broadly useful for studying memory-driven cellular decision-making in biological contexts where there is a trade-off for cells selecting from multiple phenotypic states. Such a tool can be used for predicting the response of complex systems to environmental alterations and for testing therapeutically relevant policies.
Approximations to the Solution of the Kushner-Stratonovich Equation for the Stochastic Chemostat*
Authors: Fontenele Magalhães José Augusto , Emzir Muhammad Fuady , Corona Francesco 
Published: January 2023

AbstractIn order to characterise the dynamics of a biochemical system such as the chemostat, we consider a differential description of the evolution of its state under environmental fluctuations. We present solutions to the filtering problem for a chemostat subjected to geometric Brownian motion. Under this modelling assumption, our best knowledge about the state of the system is given by its distribution in time, given the distribution of the initial state. Such a function solves a deterministic partial differential equation, the Kolmogorov forward equation. In this paper, however, we refine our knowledge about the state of the chemostat when additional information about the system is available in the form of measurements. More formally, we are interested in obtaining the distribution of the state conditional on measurements as the solution to a non-linear stochastic partial integral differential equation, the Kushner-Stratonovich equation. For the chemostat, this solution is not available in closed form, and it must be approximated. We present approximations to the solution to the Kushner-Stratonovich equation based on methods for partial differential equations. We compare the solution with a linearisation method and with a classical sequential Monte Carlo method known as the bootstrap particle filter.
Classification of Primary Angle Closure Disease by Hierarchical Cluster Analysis of Ocular Biometrics in the Dark and Light
Authors: Cho Austin , Lewinger Juan Pablo , Pardeshi Anmol A. , Aroca Galo Apolo , Torres Mina , Nongpiur Monisha , Jiang Xuejuan , McKean-Cowdin Roberta , Varma Rohit , Xu Benjamin Y. 
Published: January 2023

ABSTRACTPurposeTo investigate the classification of eyes with primary angle closure disease (PACD) based on hierarchical cluster analysis of ocular biometrics measured in the dark and light using anterior segment OCT (AS-OCT).MethodsParticipants of the Chinese American Study received complete eye exams, including gonioscopy and AS-OCT imaging, to identify primary angle closure suspects (PACS) and primary angle closure without/with glaucoma (PAC/G). Biometric parameters analyzed included angle opening distance (AOD750) and trabecular iris space area (TISA750), iris area (IA), iris thickness (IT750), iris curvature (IC), lens vault (LV), anterior chamber width (ACW) and anterior chamber depth (ACD). Hierarchical cluster analysis was performed using Ward’s method and Euclidean distance.ResultsAnalysis of 159 eyes with PACS or PAC/G produced 2 clusters in both dark and light. In both analyses, the primary cluster (N=132 in the dark, N=126 in the light) was characterized by smaller AOD750 and TISA750, greater IC, and greater LV (p<0.001). The proportion of PACS to PAC/PACG eyes was significantly different between clusters in the light (p=0.02) but not the dark cluster analysis (p=0.08). On multivariable logistic regression analysis, smaller TISA750 (OR=0.84 per 0.01μm2) and AOD750 (OR=0.93 per 0.01mm) in the light and smaller TISA750 (OR=0.86 per 0.01μm2) in the dark were significantly associated (p≤ 0.02) with higher odds of PAC/G.ConclusionCluster analysis of ocular biometrics can classify PACD eyes by disease severity. Ocular biometrics appear equally if not more strongly predictive of disease severity when measured in the light than dark. Clustering of biometric measurements obtained in the light could provide a novel method to risk-stratify patients for more severe PACD.
Depletion of theNbCORE receptor drastically improves agroinfiltration productivity in olderNicotiana benthamianaplants
Authors: Dodds Isobel , Chen Changlong , Buscaill Pierre , van der Hoorn Renier A. L. 
Published: January 2023

ABSTRACTNicotiana benthamianais increasingly used for transient gene expression to produce antibodies, vaccines, and other pharmaceutical proteins but transient gene expression is low in fully developed, 6-8wk old plants. This low gene expression is thought to be caused by the perception the cold shock protein (CSP) ofAgrobacterium tumefaciens. The CSP receptor is contested because bothNbCSPR andNbCORE have been claimed to perceive CSP. Here, we demonstrate that CSP perception is abolished in 6wk-old plants silenced forNbCORE but notNbCSPR. Importantly, olderNbCORE-silenced plants support a drastically increased level of GFP fluorescence and protein upon agroinfiltration. The drastic increase in transient protein production inNbCORE depleted plants offers new opportunities for molecular farming, where older plants with larger biomass can now be used for efficient protein expression.
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma
Authors: Xu Yuewei , Spear Sarah , Ma Yurui , Lorentzen Marc P. , Gruet Michael , McKinney Flora , Xu Yitao , Wickremesinghe Chiharu , Shepherd Madelen R , McNeish Iain , Keun Hector C. , Nijhuis Anke 
Published: January 2023

AbstractOvarian high-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer with limited therapeutic options. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Therapies disrupting the spliceosome alter cancer transcriptomes and have shown potential to improve PARP inhibitor response. Indisulam (E7070) has been identified as a molecular glue that brings splicing factor RBM39 and DCAF15 E3 ubiquitin ligase in close proximity. Exposure to indisulam induces RBM39 proteasomal degradation through DCAF15-mediated polyubiquitination and subsequent RNA splicing defects. In this study, we demonstrate that loss of RBM39 induces splicing errors in DNA damage repair genes in ovarian cancer, leading to increased sensitivity to PARP inhibitors such as olaparib. Indisulam synergized with olaparib in multiplein vitromodels of ovarian cancer regardless of PARP inhibitor sensitivity and improved olaparib response in mice bearing PARP inhibitor-resistant tumors. DCAF15 expression, but notBRCA1/2mutational status, was essential for the synergy between indisulam and olaparib, suggesting that the combination therapy may benefit patients irrespective of theirBRCA1/2status. These findings demonstrate that combining RBM39 degraders and PARP inhibitors is a promising therapeutic approach to improving PARP inhibitor response in ovarian HGSC.Graphical AbstractOne Sentence SummaryWe identified a novel drug combination that may improve PARP inhibitor response and benefit a large group of ovarian cancer patients.