bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic Landmark Detection of Human Back Surface from Depth Images via Deep Learning
Authors: Delgarmi Masumeh , Heravi Hamed , Jounghani Ali Rahimpour , Shahrezaie Abdullah , Ebrahimi Afshin , Shamsi Mousa 
Published: February 2021

AbstractStudying human postural structure is one of the challenging issues among scholars and physicians. The spine is known as the central axis of the body, and due to various genetic and environmental reasons, it could suffer from deformities that cause physical dysfunction and correspondingly reduce people’s quality of life. Radiography is the most common method for detecting these deformities and requires monitoring and follow-up until full treatment; however, it frequently exposes the patient to X-rays and ionization and as a result, cancer risk is increased in the patient and could be highly dangerous for children or pregnant women. To prevent this, several solutions have been proposed using topographic data analysis of the human back surface. The purpose of this research is to provide an entirely safe and non-invasive method to examine the spiral structure and its deformities. Hence, it is attempted to find the exact location of anatomical landmarks on the human back surface, which provides useful and practical information about the status of the human postural structure to the physician.In this study, using Microsoft Kinect sensor, the depth images from the human back surface of 105 people were recorded and, our proposed approach - Deep convolution neural network-was used as a model to estimate the location of anatomical landmarks. In network architecture, two learning processes, including landmark position and affinity between the two associated landmarks, are successively performed in two separate branches. This is a bottom-up approach; thus, the runtime complexity is considerably reduced, and then the resulting anatomical points are evaluated concerning manual landmarks marked by the operator as the benchmark. Our results showed that 86.9% of PDJ and 80% of PCK. According to the results, this study was more effective than other methods with more than thousands of training data.
Modeling ex vivo tumor-infiltrating lymphocyte expansion from established solid malignancies
Authors: Knochelmann HM , Rivera-Reyes AM , Wyatt MM , Smith AS , Chamness R , Dwyer CJ , Bobian M , Rivera GO Rangel , Horton JD , Lilly M , Rubinstein MP , Neskey DM , Paulos CM 
Published: February 2021

AbstractAdoptive transfer of tumor-infiltrating lymphocytes (TIL) elicits the regression of metastatic malignancies, yet a low proportion of patients achieve complete durable responses. The high incidence of relapse in these patients highlights the need to better understand mechanisms of tumor escape from T cell control. While melanoma has provided the foundation for developing TIL therapy, much less is known about TIL efficacy and relapse in other malignancies. We sought to investigate TIL characteristics in mouse tumors which have not been studied in this setting. Here, we expanded murine TILex vivoin IL-2 from fragments of multiple tumor models, including oral cavity cancer models of varying immunogenicity. Additionally, TIL was expanded from pmel-1 mice bearing B16 melanoma, yielding an enriched population of tumor-infiltrating TCR transgenic T cells. Murine TILs are similar to human TIL in that they express high levels of inhibitory receptors (PD-1, Tim-3, etc.) and can be expandedex vivoin IL-2 extensively. Of clinical relevance, we draw parallels between murine and patient TIL, evaluating relationships between PD-1, Lag-3, and Tim-3 on TILs from a cohort of oral cavity cancer patients. This platform can be used by labs even in the absence of clinical specimens or clean cell facilities and will be important to more broadly understand TIL phenotypes across many different malignancies.
Targeting of TP53-independent cell cycle checkpoints overcomes FOLFOX resistance in Metastatic Colorectal Cancer
Authors: Behrenbruch Corina , Foroutan Momeneh , Lind Phoebe , Smith Jai , Grandin Mélodie , Cooper Benjamin , Shembrey Carolyn , Ramm Susanne , Cowley Karla , Nikolic Iva , Luu Jennii , Cursons Joseph , Millen Rosie , Patch Ann-Marie , Huntington Nicholas D. , Puisieux Alain , Michael Michael , Knowles Brett , Thomson Benjamin NJ. , Ramsay Robert G. , Grimmond Sean M. , Simpson Kaylene , Heriot Alexander G. , Hollande Frédéric 
Published: February 2021

ABSTRACTPatients with colorectal cancer (CRC) frequently develop liver metastases during the course of their disease. A substantial proportion of them receive neoadjuvant FOLFOX (5-Fluorouracil, Oxaliplatin, Leucovorin) prior to surgery in an attempt to enable successful surgical removal of their metastases and to reduce the risk of recurrence. Yet, the majority of patients progress during treatment or recur following surgery, and molecular mechanisms that contribute to FOLFOX resistance remain poorly understood. Here, using a combination of phenotypic, transcriptomic and genomic analyses of both tumor samples derived from patients with metastatic CRC and matching patient-derived tumor organoids (PDTOs), we characterize a novel FOLFOX resistance mechanism and identify inhibitors that target this mechanism to resensitize metastatic organoids to FOLFOX. Resistant PDTOs, identified afterin vitroexposure to FOLFOX, exhibited elevated expression of E2F pathway, S phase, G2/M and spindle assembly checkpoints (SAC) genes. Similar molecular features were detected in CRLM from patients with progressive disease while under neoadjuvant FOLFOX treatment, highlighting the relevance of this finding. FOLFOX resistant PDTOs displayed inactivating mutations of TP53 and exhibited transcriptional features of P53 pathway downregulation. We found that they accumulated in early S-phase and underwent significant DNA damage during FOLFOX exposure, thereafter arresting in G2/M while they repaired their DNA after FOLFOX withdrawal. In parallel, results of a large kinase inhibitor screen indicated that drugs targeting regulators of the DNA damage response, G2M checkpoint and SAC had cytotoxic effects on PDTOs generated from patients whose disease progressed during treatment with FOLFOX. Corroborating this finding, CHK1 and WEE1 inhibitors were found to synergize with FOLFOX and sensitize previously resistant PDTOs. Additionally, targeting the SAC master regulator MPS1 using empesertib after exposure to FOLFOX, when cells accumulate in G2M, was also very effective to kill FOLFOX-resistant PDTOs. Our results indicate that targeted and timely inhibition of specific cell cycle checkpoints shows great potential to improve response rates to FOLFOX in patients with metastatic CRC, for whom therapeutic alternatives remain extremely limited.
Nitroxoline as a promising alternative drug for the treatment of Lyme disease based on anin-vitrostudy
Authors: Alvarez-Manzo Hector S. , Zhang Yumin , Shi Wanliang , Zhang Ying 
Published: February 2021

AbstractLyme disease (LD) is the most common vector-borne disease in USA and Europe and is caused byBorrelia burgdorferi. Despite proper treatment, approximately one fifth of patients will develop post-treatment LD syndrome (PTLDS), a condition which is poorly understood. One of the possible causes is thought to be due to persister forms ofB. burgdorferithat are not effectively killed by the current Lyme antibiotics. In this study, we evaluated nitroxoline, an antibiotic used to treat urinary tract infections, for its activity against a stationary-phase culture enriched with persister forms of B. burgdorferi. Nitroxoline was found to be equivalent in activity againstB. burgdorferito cefuroxime (standard Lyme antibiotic) in different experiments. Moreover, we found that the three-drug combination cefuroxime + nitroxoline + clarithromycin eradicated 98.3% of stationary phase bacteria in the drug-exposure experiment and prevented the regrowth in the subculture study after drug exposure, as well as two-drug combinations cefuroxime + nitroxoline and clarithromycin + nitroxoline. These drug combinations should be further evaluated in a LD mouse model to assess if eradication of persister forms of B. burgdorferiin-vivois possible and if so, whether nitroxoline could be repurposed as an alternative drug for the treatment of LD.
A theoretical approach to coupling the epithelial-mesenchymal transition (EMT) to extracellular matrix (ECM) stiffness via LOXL2
Authors: Deng Youyuan , Chakraborty Priyanka , Jolly Mohit Kumar , Levine Herbert 
Published: February 2021

AbstractThe epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression, being responsible in many cases for the onset of the metastatic cascade and being integral in the ability of cells to resist drug treatment. Most studies of EMT focus on its induction via chemical signals such as TGF-β or Notch ligands, but it has become increasingly clear that biomechanical features of the microenvironment such as ECM (extracellular matrix) stiffness can be equally important. Here, we introduce a coupled feedback loop connecting stiffness to the EMT transcription factor ZEB1, which acts via increasing the secretion of LOXL2 that leads to increased cross-linking of collagen fibers in the ECM. This increased cross-linking can effectively increase ECM stiffness and increase ZEB1 levels, thus setting a positive feedback loop between ZEB1 and ECM stiffness. To investigate the impact of this non-cell-autonomous effect, we introduce a computational approach capable of connecting LOXL2 concentration to increased stiffness and thereby to higher ZEB1 levels. Our results indicate that this positive feedback loop, once activated, can effectively lock the cells in a mesenchymal state.
Inference of genome 3D architecture by modeling overdispersion of Hi-C data
Authors: Varoquaux Nelle , Noble William S. , Vert Jean-Philippe 
Published: February 2021

We address the challenge of inferring a consensus 3D model of genome architecture from Hi-C data. Existing approaches most often rely on a two step algorithm: first convert the contact counts into distances, then optimize an objective function akin to multidimensional scaling (MDS) to infer a 3D model. Other approaches use a maximum likelihood approach, modeling the contact counts between two loci as a Poisson random variable whose intensity is a decreasing function of the distance between them. However, a Poisson model of contact counts implies that the variance of the data is equal to the mean, a relationship that is often too restrictive to properly model count data.We first confirm the presence of overdispersion in several real Hi-C data sets, and we show that the overdispersion arises even in simulated data sets. We then propose a new model, called Pastis-NB, where we replace the Poisson model of contact counts by a negative binomial one, which is parametrized by a mean and a separate dispersion parameter. The dispersion parameter allows the variance to be adjusted independently from the mean, thus better modeling overdispersed data. We compare the results of Pastis-NB to those of several previously published algorithms: three MDS-based methods (ShRec3D, ChromSDE, and Pastis-MDS) and a statistical methods based on a Poisson model of the data (Pastis-PM). We show that the negative binomial inference yields more accurate structures on simulated data, and more robust structures than other models across real Hi-C replicates and across different resolutions.A Python implementation of Pastis-NB is available athttps://github.com/hiclib/pastisunder the BSD licenseSupplementary information is available athttps://nellev.github.io/pastisnb/
Mathematical model reveals that heterogeneity in the number of ion transporters regulates the fraction of mouse sperm capacitation
Authors: Aguado-García Alejandro , Priego-Espinosa Daniel A. , Aldana Andrés , Darszon Alberto , Martínez-Mekler Gustavo 
Published: February 2021

AbstractCapacitation is a complex maturation process mammalian sperm must undergo in the female genital tract to be able to fertilize an egg. This process involves, amongst others, physiological changes in flagellar beating pattern, membrane potential, intracellular ion concentrations and protein phosphorylation. Typically, in a capacitation medium, only a fraction of sperm achieve this state. The cause for this heterogeneous response is still not well understood and remains an open question. Here, one of our principal results is to develop a discrete regulatory network, with mostly deterministic dynamics in conjunction with some stochastic elements, for the main biochemical and biophysical processes involved in the early events of capacitation. The model criterion for capacitation requires the convergence of specific levels of a select set of nodes. Besides reproducing several experimental results and providing some insight on the network interrelations, the main contribution of the model is the suggestion that the degree of variability in the total amount and individual number of ion transporters among spermatozoa regulates the fraction of capacitated spermatozoa. This conclusion is consistent with recently reported experimental results. Based on this mathematical analysis, experimental clues are proposed for the control of capacitation levels. Furthermore, cooperative and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.Author summaryFertilization is one of the fundamental processes for the preservation of life. In mammals, sperm undergo a complex process during their passage through the female tract known as capacitation, which enables them for fertilization. At the present time, it is accepted from experimental observation, though not understood, that only a fraction of the sperm is capacitated. In this work, by means of a network mathematical model for regulatory sperm intracellular signaling processes involved in mice capacitation, we find that the variability in the distribution of the number of ion transporters intervenes in the regulation of the capacitation fraction. Experimental verification of this suggestion could open a line of research geared to the regulation of the degree of heterogeneity in the number of ion transporters as a fertility control. The model also uncovers, throughin silicooveractivation and loss of function of network nodes, synergetic traits which again call for experimental verification.
LncRNA SNHG1 suppresses LPS-induced acute lung injury by regulating miR-421/TIMP3 axis
Authors: Jiang Zeyu , Tan Jinyi , Yuan Yan , Shen Jiang , Chen Yan 
Published: February 2021

AbstractExtensive evidence has revealed the crucial roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). This study aimed to explore the mechanism of lncRNA SNHG1 in lipopolysaccharides (LPS)-induced ALI. RT-qPCR was employed to test the levels of SNHG1, miR-421 and TIMP3 in A549 cells. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. ELISA assay was adopted to examine the levels of inflammatory-related cytokines, including IL-1β, IL-6 and TNF-α. The binding sequences of miR-421 and SNHG1 or TIMP3 were predicted using starBase software. Then dual-luciferase reporter and RIP assays were adopted to verify the interaction between miR-421 and SNHG1 or TIMP3. The protein level of TIMP3 was measured by western blotting. It was found that LPS stimulation downregulated SNHG1 level and SNHG1 addition decreased viability, and induced apoptosis as well as promoted inflammatory responses in LPS-treated A549 cells. SNHG1 could sponge miR-421 and SNHG1 protected A549 cells from LPS-induced injury via inhibiting miR-421. Moreover, TIMP3 was a target of miR-421. MiR-421 silence protected A549 cells against the LPS-triggered inhibition in viability, and promotion in apoptosis and inflammatory responses. SNHG1 could upregulate TIMP3 through acting as a ceRNA of miR-421 in A549 cells. Altogether, the present study elaborated that SNHG1 inhibited LPS-stimulated ALI by modulating the miR-421/TIMP3 axis.
Little evidence the standard genetic code is optimized for resource conservation
Authors: Rozhoňová Hana , Payne Joshua L. 
Published: February 2021

AbstractSelection for resource conservation can shape the coding sequences of organisms living in nutrient-limited environments. Recently, it was proposed that selection for resource conservation, specifically for nitrogen and carbon content, has also shaped the structure of the standard genetic code, such that the missense mutations it allows tend to cause small increases in the number of nitrogen and carbon atoms in amino acids. Moreover, it was proposed that this optimization is not confounded by known optimizations of the standard genetic code, such as for polar requirement or hydropathy. We challenge these claims. We show the proposed optimization for nitrogen conservation is highly sensitive to choice of null model and the proposed optimization for carbon conservation is confounded by the known conservative nature of the standard genetic code with respect to the molecular volume of amino acids. There is therefore little evidence the standard genetic code is optimized for resource conservation.
A partially nested cortical hierarchy of neural states underlies event segmentation in the human brain
Authors: Geerligs Linda , Gözükara Dora , Oetringer Djamari , Campbell Karen , van Gerven Marcel , Güçlü Umut 
Published: February 2021

AbstractA fundamental aspect of human experience is that it is segmented into discrete events. This may be underpinned by transitions between distinct neural states. Using an innovative data-driven state segmentation method, we investigate how neural states are organized across the cortical hierarchy and where in the cortex neural state boundaries and perceived event boundaries overlap. Our results show that neural state boundaries are organized in a temporal cortical hierarchy, with short states in primary sensory regions, and long states in lateral and medial prefrontal cortex. State boundaries are shared within and between groups of brain regions that resemble well-known functional networks. Perceived event boundaries overlap with neural state boundaries across large parts of the cortical hierarchy, particularly when those state boundaries demarcate a strong transition or are shared between brain regions. Taken together, these findings suggest that a partially nested cortical hierarchy of neural states forms the basis of event segmentation.
What The Brain Does As We Speak
Authors: Forseth KJ , Pitkow X , Fischer-Baum S , Tandon N 
Published: February 2021

AbstractLanguage is a defining human behavior and is dependent on networks interactions amongst broadly distributed neuronal substrates. Transient dynamics between language regions that underpin speech production have long been postulated, yet have proven challenging to evaluate empirically. We used direct intracranial recordings during single word production to create a finely resolved spatiotemporal atlas (134 patients, 25810 electrodes, 40278 words) of the entire language-dominant cortex and used this to derive single-trial state-space sequences of network motifs. We derived 5 discrete neural states during the production of each word, distinguished by unique patterns of distributed cortical interaction. This interactive model was significantly better than a model of the same design but lacking interactions between regions in explaining observed activity. Our results eschew strict functional attribution to localized cortical populations, supporting instead the idea that cognitive processes are better explained by distributed metastable network states.
Ancient genomes reveal hybridisation between extinct short-faced bears and the extant spectacled bear (Tremarctos ornatus)
Authors: Salis Alexander T , Gower Graham , Schubert Blaine W. , Soibelzon Leopoldo H. , Heiniger Holly , Prieto Alfredo , Prevosti Francisco J. , Meachen Julie , Cooper Alan , Mitchell Kieren J. 
Published: February 2021

SummaryTwo genera and multiple species of short-faced bear from the Americas went extinct during or toward the end of the Pleistocene, and all belonged to the endemic New World subfamily Tremarctinae [1-7]. Two of these species were giants, growing in excess of 1,000 kg [6, 8, 9], but it remains uncertain how these extinct bears were related to the sole surviving short-faced bear: the spectacled bear (Tremarctos ornatus). Ancient mitochondrial DNA has recently suggested phylogenetic relationships among these lineages that conflict with interpretations based on morphology [1, 10-12]. However, widespread hybridisation and incomplete lineage sorting among extant bears mean that the mitochondrial phylogeny frequently does not reflect the true species tree [13, 14]. Here we present ancient nuclear genome sequences from representatives of the two extinct short-faced bear genera,ArctotheriumandArctodus. Our new data support a third hypothesis for the relationships among short-faced bears, which conflicts with existing mitochondrial and morphological data. Based on genome-wide D-statistics, we suggest that the extant spectacled bear derives substantial ancestry from Pleistocene hybridisation with an extinct short-faced bear lineage, resulting in a discordant phylogenetic signal between the mitochondrion and portions of the nuclear genome.
LevioSAM: Fast lift-over of alternate reference alignments
Authors: Mun Taher , Chen Nae-Chyun , Langmead Ben 
Published: February 2021

AbstractMotivationAs more population genetics datasets and population-specific references become available, the task of translating (“lifting”) read alignments from one reference coordinate system to another is becoming more common. Existing tools generally require a chain file, whereas VCF files are the more common way to represent variation. Existing tools also do not make effective use of threads, creating a post-alignment bottleneck.ResultsLevioSAM is a tool for lifting SAM/BAM alignments from one reference to another using a VCF file containing population variants. LevioSAM uses succinct data structures and scales efficiently to many threads. When run downstream of a read aligner, levioSAM completes in less than 13% the time required by an aligner when both are run with 16 threads.Availabilityhttps://github.com/alshai/levioSAMContacttmun1@jhu.edu,langmea@cs.jhu.edu
Cell Rearrangement Generates Pattern Emergence as a Function of Temporal Morphogen Exposure
Authors: Fulton Timothy , Spiess Kay , Thomson Lewis , Wang Yuxuan , Clark Bethan , Hwang Seongwon , Paige Brooks , Verd Berta , Steventon Benjamin 
Published: February 2021

AbstractAs tissues elongate, cell rearrangement alters positional information in manner that must be accounted for to generate gene expression pattern. How this is achieved during paraxial mesoderm elongation is unknown. By reverse-engineering gene regulatory networks that predict single cell expression trajectories across the tissue, we find a network capable of recapitulating the full range of dynamic differentiation profiles observed bothin vivoandin vitro. Simulating gene expression profiles onin totocell tracking data sets reveal that temporal exposure to Wnt and FGF is generated by cell movement. The absence of reversal in gene expression towards a more premature gene expression state predicts the generation of aberrant tbx6 expression in the posterior progenitor zone that we then confirm by quantitative single cell imaging. Taken together, these results demonstrate cell rearrangement tunes the dynamics of mesoderm progenitor differentiation to generate pattern emergence as a function of temporal Wnt and FGF exposure.