bluuebunny/crossref_metadata_2025_split huggingface dataset:
CIRC_0085323 SILENCING INHIBITS TNF-Α-INDUCED NORMAL HUMAN COLONIC EPITHELIAL CELL INFLAMMATION AND APOPTOSIS THROUGH THE MIR-495-3P/TRAF3 AXIS
Authors: An Qi , Yang Shengsen , Tao Jianan , Yang Mengdi , Ma Zhenqi , Gao Qian , Wang Xuehong 
Published: October 2023

ABSTRACT

Background: Previous data have suggested the involvement of circular RNA (circRNA) in ulcerative colitis (UC) development. However, the role and mechanism of circ_0085323 in UC occurrence have not been reported. Methods: Normal human colonic epithelial cells (NCM460) were treated with TNF-α to simulate UC-like cell inflammation and injury in vitro. The expression of circ_0085323, microRNA-495-3p (miR-495-3p), and TNF receptor–associated factor 3 (TRAF3) was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blotting analysis. Cell viability, cell proliferation, and cell apoptosis were investigated by cell counting kit-8 assay, 5-ethynyl-29-deoxyuridine assay, and flow cytometry analysis, respectively. IL-1β, IL-6, and IL-8 production were analyzed by enzyme-linked immunosorbent assays. Lactate dehydrogenase activity was assessed by a lactate dehydrogenase activity detection assay. The interactions among circ_0085323, miR-495-3p, and TRAF3 were identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0085323 was overexpressed in the colonic mucosal tissues of UC patients and TNF-α–stimulated NCM460 cells. Circ_0085323 knockdown relieved TNF-α–induced inhibitory effect on the proliferation of NCM460 cells and promoting effects on cell apoptosis and inflammation. Circ_0085323 acted as a miR-495-3p sponge, and the effects of circ_0085323 silencing on TNF-α–induced NCM460 cell injury were attenuated by decreasing miR-495-3p expression. TRAF3 was targeted by miR-495-3p, and circ_0085323 combined with miR-495-3p to regulate TRAF3. TRAF3 depletion not only alleviated TNF-α–induced NCM460 cell damage but also partially revoked the effect of circ_0085323 silencing combined with miR-495-3p depletion on TNF-α–induced NCM460 cell injury. Conclusions: Circ_0085323 knockdown ameliorated TNF-α–induced NCM460 cell injury by regulating the miR-495-3p/TRAF3 axis, which suggested that circ_0085323 might be a therapeutic target for UC.
From 6-wk Lungs to 6 y: Increasing the Donor Pool for Pediatric Lung Transplantation
Authors: Purmessur Rushmi , Spencer Helen , Onwuka Nkechi Bliss , Muthialu Nagarajan , Berman Marius 
Published: October 2023

Background.
Lung transplantation in the pediatric population is a challenge. With the donor pool being so small and lungs from young donors rare and precious, every organ available needs to be utilized to its best potential.

Case.
Here, we describe the case of a 6-wk-old donor of double lungs to a 5-mo-old baby girl diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins. The recipient is doing very well, 6 y after the transplant, now following normal growth.

Discussion.
The challenges facing pediatric cardiothoracic transplantation in terms of organ supply and demand are enormous.

Conclusions.
In this article, we discuss some of the issues around the shortage of organs and alternatives to increase the organ donor pool.
A fatal case of necrotizing fasciitis by Aeromonas jandaei
Authors: Anil Anjali , Kumar Mani Bhushan , Chauhan Sachin , Ray Pallab , Dahiya Divya , Angrup Archana 
Published: October 2023

Introduction : Necrotizing soft tissue infections are associated with an extremely fulminating course, owing to its rapid destruction of tissue planes underlying the skin. Aeromonas associated monomicrobial NSTIs are usually associated with exposure to fresh water, via trauma, trivial abrasions or even reptile bites, particularly among agricultural workers and fish handlers. Albeit uncommon in incidence, urgent medical and surgical intervention is required once diagnosis is reached.
Case report : A 40-year-old male patient, known case of alcoholic liver disease, presented to the emergency department with pain and diffuse swelling of bilateral lower limbs, which quickly progressed to form blackish discolouration and blebs. Blood for preliminary haematological and biochemical investigations, as well as fluid draining from blebs was sent for microbiological investigation. The gram stain revealed occasional pus cells and gram-negative bacilli, pure growth in aerobic culture was identified as Aeromonasjandaei by Matrix-assisted laser desorption/ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). Patient was started on empirical antimicrobials, though lesions continued to progress and he ultimately succumbed within 24 hours of his hospital stay.
Conclusion : As appropriate antimicrobial therapy and early surgical intervention are required for management of the same, occupational exposure and the fulminant course should raise suspicion of likelihood of Aeromonas associated infections.
Characterizing Acute Low Back Pain in a Community-Based Cohort
Authors: Burke Colleen , Taylor Kenneth A. , Fillipo Rebecca , George Steven Z. , Kapos Flavia P. , Danyluk Stephanie , Kingsbury Carla A. , Seebeck Kelley , Lewis Christopher E. , Ford Emily , Plez Cecilia , Kosinski Andrzej S. , Brown Michael C. , Goode Adam P. 
Published: October 2023

AbstractAcute low back pain (LBP) is a common experience, however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, three acute LBP severity categorization definitions were used based on LBP frequency combined with either 1) pain impact frequency (impact-based) or 2) pain intensity (intensity-based), as well as LBP pain interference frequency (interference only-based) severity categories. The purpose of this manuscript is to describe and then compare these acute LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological. This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios for categorical variables and Hedges’gfor continuous variables. Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. The interference-based category did not capture as much variability between acute LBP severity categories. This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute LBP. The robust differences observed between these categorization approaches suggest that how we define acute LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic LBP.
Data Extraction for Evidence Synthesis Using a Large Language Model: A Proof-of-Concept Study
Authors: Gartlehner G , Kahwati L , Hilscher R , Thomas I , Kugley S , Crotty K , Viswanathan M , Nussbaumer-Streit B , Booth G , Erskine N , Konet A , Chew R 
Published: October 2023

AbstractData extraction is a crucial, yet labor-intensive and error-prone part of evidence synthesis. To date, efforts to harness machine learning for enhancing efficiency of the data extraction process have fallen short of achieving sufficient accuracy and usability. With the advent of Large Language Models (LLMs), new possibilities have emerged to increase efficiency and accuracy of data extraction for evidence synthesis. The objective of this proof-of-concept study was to assess the performance of an LLM (Claude 2) in extracting data elements from published studies, compared with human data extraction as employed in systematic reviews. Our analysis utilized a convenience sample of 10 English-language, open-access publications of randomized controlled trials included in a single systematic review. We selected 16 distinct types of data, posing varying degrees of difficulty (160 data elements across 10 studies). We used the browser version of Claude 2 to upload the portable document format of each publication and then prompted the model for each data element. Across 160 data elements, Claude 2 demonstrated an overall accuracy of 96.3% with a high test-retest reliability (replication 1: 96.9%; replication 2: 95.0% accuracy). Overall, Claude 2 made 6 errors on 160 data items. The most common errors (n=4) were missed data items. Importantly, Claude 2’s ease of use was high; it required no technical expertise or training data for effective operation. Based on findings of our proof-of-concept study, leveraging LLMs has the potential to substantially enhance the efficiency and accuracy of data extraction for evidence syntheses.
A comparison of Markov and mechanistic models for STH prevalence projections in the context of survey design
Authors: Eyre Max T. , Bulstra Caroline A. , Johnson Olatunji , de Vlas Sake J. , Diggle Peter J. , Fronterrè Claudio , Coffeng Luc E. 
Published: October 2023

AbstractGlobally, there are over one billion people infected with soil-transmitted helminths (STHs), mostly living in marginalised settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The WHO recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education, and the delivery of preventive chemotherapy (PC) to school age children delivered through schools. Progress of STH control programmes is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these two methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not reduce despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other NTDs.
From Sensory to Perceptual Manifolds: The Twist of Neural Geometry
Authors: Ma Heng , Jiang Longsheng , Liu Tao , Liu Jia 
Published: October 2023

AbstractClassification constitutes a core cognitive challenge for both biological and artificial intelligence systems, with many tasks potentially reducible to classification problems. Here we investigated how the brain categorizes stimuli that are not linearly separable in the physical world by analyzing the geometry of neural manifolds in high-dimensional neural space, formed by macaques’ V2 neurons during a classification task on the orientations of motion-induced illusory contours. We identified two related but distinct neural manifolds in this high-dimensional neural space: the sensory and perceptual manifolds. The sensory manifold was embedded in a 3-D subspace defined by three stimulus features, where contour orientations remained linearly inseparable. However, through a series of geometric transformations equivalent to twist operations, this 3-D sensory manifold evolved into a 7-D perceptual manifold with four additional axes, enabling the linear separability of contour orientations. Both formal proof and computational modeling revealed that this dimension expansion was facilitated by nonlinear mixed selectivity neurons exhibiting heterogeneous response profiles. These findings provide insights into the mechanisms by which biological neural networks increase the dimensionality of representational spaces, illustrating how perception arises from sensation through the lens of neural geometry.
Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions
Authors: Rogers Zachary J. , Colombani Thibault , Khan Saad , Bhatt Khushbu , Nukovic Alexandra , Zhou Guanyu , Woolston Benjamin M. , Taylor Cormac T. , Gilkes Daniele M. , Slavov Nikolai , Bencherif Sidi A. 
Published: October 2023

AbstractOxygen (O2) tension plays a key role in tissue function and pathophysiology. O2-controlled cell culture, in which the O2concentration in an incubator’s gas phase is controlled, is an indispensable tool to study the role of O2in vivo. For this technique, it is presumed that the incubator setpoint is equal to the O2tension that cells experience (i.e., pericellular O2). We discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0.0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2consumption is the driving factor. RNA-seq revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to anoxic exposure followed by rapid reoxygenation. To better understand the relationship between incubator gas phase and pericellular O2tensions, we developed a reaction-diffusion model that predicts pericellular O2tensiona priori. This model revealed that the effect of cellular O2consumption is greatest in smaller volume culture vessels (e.g.,96-well plate). By controlling pericellular O2tension in cell culture, we discovered that MCF7 cells have stronger glycolytic and glutamine metabolism responses in anoxiavs.hypoxia. MCF7 also expressed higher levels ofHIF2A,CD73,NDUFA4L2,etc.and lower levels ofHIF1A,CA9,VEGFA, etc.in response to hypoxiavs.anoxia. Proteomics revealed that 4T1 cells had an upregulated epithelial-to-mesenchymal transition (EMT) response and downregulated reactive oxygen species (ROS) management, glycolysis, and fatty acid metabolism pathways in hypoxiavs.anoxia. Collectively, these results reveal that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable to model hypoxia. We demonstrate that controlling atmospheric O2tension in cell culture incubators is insufficient to control O2in cell culture and introduce the concept ofpericellular O2-controlled cell culture.
Comparing different methods of estimating GWAS heritability with a new approach using only summary statistics
Authors: Salehi Ehsan 
Published: October 2023

ABSTRACTSo far SNP heritability (;variance explained by all SNP s used in genome-wide association study) has explained most of genetic variation for many traits but still there is a gap between GWAS heritability (; variance explained by genome-wide significant SNPs) andthat is named hidden heritability.There are several methods for estimating(linear_mixed_model (LMM), PRS, multiple_linear_regression (MLR) and simple_linear_regression(SLR)). However, it is unclear which methods are more accurate under different circumstances. This study proposes a PRS based method for estimatingthat uses pseudo summary statistics. It compares this method with existing methods using both simulated and real data (10 traits from UKBB) to determine when they are realistic and can be trusted as a final estimate.Simulation results showed that PRS-based methods underestimatenear 20% when considering all causal SNPs. But they are relatively accurate when using a subset of causal SNPs. Their performance is much better than SLR method for all 10 traits, although when applied to real data, they do not follow a stable trend of overestimation or underestimation compared to the base model (LMM).My suggestion is to use LMM or adjusted_R2from MLR for reportingwhen an independent data set is available. In cases where only summary statistics is available, the PRS-PSS is relatively an accurate alternative, especially compared to SLR, which tends to overestimateby 20-50% when applying it on real data.
Colon cancer arises from differentiated cell lineages in the context of inflammation
Authors: Verhagen Mathijs P. , Joosten Rosalie , Schmitt Mark , Välimäki Niko , Sacchetti Andrea , Rajamäki Kristiina , Choi Jiahn , Procopio Paola , Silva Sara , van der Steen Berdine , van den Bosch Thierry P.P. , Seinstra Danielle , Doukas Michail , Augenlicht Leonard H. , Aaltonen Lauri A. , Fodde Riccardo 
Published: October 2023

AbstractAccording to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, was shown to suppress intestinal stemness. Here, we employed Paneth cells (PCs) as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation. Upon inflammation, PC-specificApcmutations led to intestinal tumors reminiscent not only of those arising in inflammatory bowel disease (IBD) patients but also of a larger fraction of sporadic colon cancers. The latter is likely due to the inflammatory consequences of Western-style dietary habits, the major colon cancer risk factor. Computational methods designed to predict the cell-of-origin of cancer confirmed that, in a substantial fraction of sporadic colon cancers the cells-of-origin are secretory lineages and not stem cells.One-Sentence SummarySecretory cell lineages trigger tumor formation in the context of the major etiologic colon cancer risk factors.
Nucleolin-RNA interaction modulates rotavirus replication
Authors: Hernández-Guzmán Jey , Arias Carlos F. , López Susana , Sandoval-Jaime Carlos 
Published: October 2023

AbstractRotavirus infection is a leading cause of gastroenteritis in children worldwide, the genome of this virus is composed of eleven segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, on rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 5-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA binding domains. Under these conditions, viral production increased by 1.54-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all eleven RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through direct interaction with the viral RNAs by sequences forming G4 structures.ImportanceViruses rely on cellular proteins to carry on their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA, and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.
Inversions Can Accumulate Balanced Sexual Antagonism: Evidence from Simulations and Drosophila Experiments
Authors: McAllester Christopher S. , Pool John E. 
Published: October 2023

AbstractChromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion associated with one haplotype can reduce the fitness load incurred by generating recombinant offspring, reinforcing its linkage to the haplotype and enabling both haplotypes to accumulate more antagonistic variants than expected otherwise. We develop and apply a forward simulator to examine these dynamics under a tradeoff between survival and male display. These simulations indeed generate inversion-associated haplotypes with opposing sex-specific fitness effects. Antagonism strengthens with time, and can ultimately yield karyotypes at surprisingly predictable frequencies, with striking genotype frequency differences between sexes and between developmental stages. To test whether this model may contribute to well-studied yet enigmatic inversion polymorphisms inDrosophila melanogaster, we track inversion frequencies in laboratory crosses to test whether they influence male reproductive success or survival. We find that two of the four tested inversions show significant evidence for the tradeoff examined, withIn(3R)Kfavoring survival andIn(3L)Okfavoring male reproduction. In line with the apparent sex-specific fitness effects implied for both of those inversions,In(3L)Okwas also found to be less costly to the viability and/or longevity of males than females, whereasIn(3R)Kwas more beneficial to female survival. Based on this work, we expect that balancing selection on antagonistically pleiotropic traits may provide a significant and underappreciated contribution to the maintenance of natural inversion polymorphism.