bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Efficacy of 2-Needle Joint Lavage for Osteoarthritis-Related Knee Pain and Predictors of Response Based on Knee MRI Osteoarthritis Knee Score: A Medical Records Review Study
Authors: Li Shiyao , Jiang Xiaohan , Wang Junnan , Chen Yang , Shi Rongchao , Ding Feier , Chu Lingyan , Sun Tao 
Published: October 2023

Background
Knee osteoarthritis (OA) is notoriously difficult to treat. Pain is the key symptom for patients to seek medical attention. This study aimed to evaluate the therapeutic efficacy of joint lavage (JL) for OA-related knee pain and to explore the knee pathological changes detected by magnetic resonance imaging that may affect the prognosis of patients who received JL.

Methods
Eighty-two hospitalized patients who were diagnosed with knee OA and received JL in our department were finally enrolled in this study. The patients' clinical data including Numeric Rating Scale (NRS), Western Ontario and McMaster Osteoarthritis Index pain subscale, analgesic medication usage, adverse events, and magnetic resonance imaging data of the affected knee joint scored by the MRI Osteoarthritis Knee Score were recorded and analyzed.

Results
The NRS scores significantly decreased after JL and remained steady until 6 months (p < 0.001). The Western Ontario and McMaster Osteoarthritis Index pain scores and the percentage of patients who needed analgesic medication significantly decreased at 6 months compared with baseline (p < 0.001). At 6 months after JL, 51 of the 82 patients experienced ≥50% improvement in their NRS scores (effective). Multivariate binary logistic regression analysis revealed that duration of pain (odds ratio [OR], 1.022; 95% confidence interval [CI], 1.003–1.042; p = 0.024), bone marrow lesion score (OR, 1.221; 95% CI, 1.028–1.450; p = 0.023), and cartilage loss score (OR, 1.272; 95% CI, 1.021–1.585; p = 0.032) significantly influenced the therapeutic efficacy of JL.

Conclusions
JL treatment can significantly alleviate the OA-related knee pain in at least 6 months. JL tends to provide limited benefit for patients with long duration of pain, serious bone marrow lesions, and severe cartilage loss.
Innovative Research Methods
Authors: Green Ellen P. , Dong Yue , Shah Nilay D. 
Published: October 2023

Summary Statement
Health care policies have the potential to improve patient outcomes, access to care, and reduce health disparities. However, new policy is often tested in the field, where unintended consequences are paid for by patients. In this perspective, we argue that health care simulations, which can elucidate the potential for policy to hinder clinicians' ability to provide high-quality care, are a complement to large-scale policy evaluations in the field.
Differential Vessel features according to the Pathophysiologic Type of Intracranial Atherosclerosis
Authors: Kim Hyung Jun , Cho Hwan-Ho , Park Hyunjin , Choi Jong-Un , Song Ha-Na , Lee Ji-Eun , Baek In-Young , Chung Jong-Won , Bang Oh Young , Kim Gyeong-Moon , Seo Woo-Keun 
Published: October 2023

ABSTRACTBACKGROUNDPrevious studies have assessed the relationship between vessel tortuosity and atherosclerosis in long vessel segments. We evaluated the relationship between tortuosity and parent artery atherosclerotic disease (PAD) in short vessel segments, and the differences between the PAD and branch atheromatous disease (BAD).METHODSComputerized analysis of the images provided quantitative vessel features at every 0.2841 mm interval point of the vessel’s centerline. The vessel features that reflect vessel tortuosity include curvature and torsion. To analyze the local features of the vessels, the middle cerebral artery (MCA) was divided into three segments.RESULTSA total of 59 and 77 patients with PAD and BAD of the MCA were included. Stenotic segments were isolated in 33 patients with PAD and were mostly located in the distal segment; stenotic segments were also isolated in 24 patients with BAD and were mostly located in the middle segment (P=0.074). The curvature of the stenotic segment of PAD was significantly increased compared to the non-stenotic segments of the ipsilateral (0.29 ± 0.08 for the stenotic segment vs. 0.26 ± 0.07 for the non-stenotic segment,P=0.048), and increased but not significant compared to the stenotic segment of BAD (0.29 ± 0.08 for PAD vs. 0.26 ± 0.05 for BAD,P=0.083). In the multivariable regression analysis, curvature (odds ratio, 2.136; 95% confidence interval, 1.251–3.645;P=0.005) was associated with PAD.CONCLUSIONSOur findings suggested that increased tortuosity is associated with the development of PAD and that PAD and BAD have different vessel features and plaque locations and thereby, different pathophysiological mechanisms.
Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog
Authors: Coate Katie C. , Ramnanan Christopher J. , Smith Marta , Winnick Jason J. , Kraft Guillaume , Irimia-Dominguez Jose , Farmer Ben , Donahue E. Patrick , Roach Peter J. , Cherrington Alan D. , Edgerton Dale S. 
Published: October 2023

AbstractGlucagon rapidly and profoundly simulates hepatic glucose production (HGP), but for reasons which are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course and relevance (to metabolic flux) of glucagon-mediated molecular events in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a 6-fold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group glucose remained at basal while in the other glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) but only partially sustained increase in hepatic cAMP over 4h, a continued elevation in G6P, and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis and HGP increased rapidly, peaking at 30 min, then returned to baseline over the next three hours (although glucagon’s stimulatory effect on HGP was sustained relative to the hyperglycemic control group). Hepatic gluconeogenic flux did not increase due to lack of glucagon effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, and downregulation of genes involved in extracellular matrix assembly and development.
A portable and wind resistant drift fence array for arid environments
Authors: Camper Benjamin T. , Laughlin Zachary T. , Kanes Andrew S. , Manuel Riley T. , Bewick Sharon A. 
Published: October 2023

AbstractDrift fences are passive trapping systems for both small vertebrates and large invertebrates. Most drift fence designs are semi-permanent or otherwise difficult to transport after initial installation. While these designs are effective for replicate trapping through time, most designs lack portability. Here, we propose a novel drift fence design that uses PVC pipes and fiberglass mesh screen. The combination of hollow PVC pipes and mesh screen creates a lightweight system that facilitates rapid deployment and redeployment across locations. Since the PVC pipes can be filled with topsoil from the site of trap installation, enhanced portability does not come at the cost of fence stability or wind resistance. We provide results on trap performance in a New Mexico flatland desert and discuss the efficacy and cost of our proposed drift fence design.
Metabolic imaging across scales reveals distinct prostate cancer phenotypes
Authors: Sushentsev Nikita , Hamm Gregory , Flint Lucy , Birtles Daniel , Zakirov Aleksandr , Richings Jack , Ling Stephanie , Tan Jennifer Y. , McLean Mary A. , Ayyappan Vinay , Menih Ines Horvat , Brodie Cara , Miller Jodi L. , Mills Ian G. , Gnanapragasam Vincent J. , Warren Anne Y. , Barry Simon T. , Goodwin Richard J.A. , Barrett Tristan , Gallagher Ferdia A. 
Published: October 2023

AbstractHyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we have used a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as tumours containing cribriform and non-cribriform Gleason pattern 4 disease. The elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by their lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify novel metabolic phenotypes in prostate cancer.
Discovery of Ancestry-specific Variants Associated with Clopidogrel Response among Caribbean Hispanics
Authors: Yang Guang , González Pablo , Moneró Mariangeli , Carrasquillo Kelvin , Renta Jessicca Y. , Hernandez-Suarez Dagmar F. , Botton Mariana R. , Melin Kyle , Scott Stuart A. , Ruaño Gualberto , Roche-Lima Abiel , Alarcon Cristina , Ritchie Marylyn D. , Perera Minoli A. , Duconge Jorge 
Published: October 2023

AbstractBackgroundHigh on-treatment platelet reactivity (HTPR) with clopidogrel is predictive of ischemic events in adults with coronary artery disease. Despite strong data suggesting HTPR varies with ethnicity, including clinical and genetic variables, no genome-wide association study (GWAS) of clopidogrel response has been performed among Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of Caribbean Hispanic cardiovascular patients from Puerto Rico.MethodsLocal Ancestry inference (LAI) and traditional GWASs were performed on a cohort of 511 clopidogrel-treated patients, stratified based on their P2Y12 reaction units (PRU) into responders and non-responders (HTPR).ResultsThe LAI GWAS identified variants within theCYP2C19region associated with HTPR, predominantly driven by individuals of European ancestry and absent in those with native ancestry. Incorporating local ancestry adjustment notably enhanced our ability to detect associations. While no loci reached traditional GWAS significance, three variants showed suggestive significance at chromosomes 3, 14 and 22 (OSBPL10rs1376606,DERL3rs5030613, andRGS6rs9323567). In addition, a variant in theUNC5Cgene on chromosome 4 was associated with an increased risk of HTPR. These findings were not identified in other cohorts, highlighting the unique genetic landscape of Caribbean Hispanics.ConclusionThis is the first GWAS of clopidogrel response in Hispanics, confirming the relevance of theCYP2C19cluster, particularly among those with European ancestry, and also identifying novel markers in a diverse patient population. Further studies are warranted to replicate our findings in other diverse cohorts and meta-analyses.
Cortical parenchyma wall width (CPW) regulates root metabolic cost and maize performance under suboptimal water availability
Authors: Sidhu Jagdeep Singh , Lopez-Valdivia Ivan , Strock Christopher F. , Schneider Hannah M. , Lynch Jonathan P. 
Published: October 2023

AbstractWe describe how increased root cortical parenchyma wall width (CPW) can improve tolerance to drought stress in maize by reducing the metabolic costs of soil exploration. Significant variation (1.0 to 5.0 µm) for CPW was observed within maize germplasm. The functional-structural modelRootSlicepredicts that increasing CPW from 2 to 4 µm is associated withca.15% reduction in root cortical cytoplasmic volume, respiration rate, and nitrogen content. Analysis of genotypes with contrasting CPW grown with and without water stress in the field confirms that increased CPW is correlated with ca. 32 to 42% decrease in root respiration. Under water stress in the field, increased CPW is correlated with 125% increased stomatal conductance, 325% increased leaf CO2assimilation rate, 73 to 78% increased shoot biomass, and 92 to 108% increased grain yield. CPW was correlated with leaf mesophyll midrib parenchyma wall width, indicating pleiotropy. GWAS analysis identified candidate genes underlying CPW.OpenSimRootmodeling predicts that a reduction in root respiration due to increased CPW would also benefit maize growth under suboptimal nitrogen, which requires empirical testing. We propose CPW as a new phene that has utility under edaphic stress meriting further investigation.Significance StatementSuboptimal water availability is a primary constraint for global crop production that is intensifying due to climate change. The metabolic cost of soil exploration is a critical factor in plant performance under suboptimal water availability. This study highlights how increased root cortical parenchyma wall width (CPW) reduces root metabolic cost and improves crop adaptation to water deficit. Modeling results also indicate that increased CPW would be beneficial under suboptimal nitrogen availability. Therefore, CPW is a promising target for breeding crops with improved water and nitrogen use efficiency.
Mutation-specific CAR T cells as precision therapy for IGLV3-21R110expressing high-risk chronic lymphocytic leukemia
Authors: Märkl Florian , Schultheiß Christoph , Ali Murtaza , Chen Shih-Shih , Egli Lukas , Mietz Juliane , Chijioke Obinna , Paschold Lisa , Spajic Sebastijan , Holtermann Anne , Dörr Janina , Stock Sophia , Piseddu Ignazio , Anz David , Minden Marcus Dühren-von , Zhang Tianjiao , Nerreter Thomas , Hudecek Michael , Chiorazzi Nicholas , Kobold Sebastian , Binder Mascha 
Published: October 2023

AbstractThe concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we used a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We developed murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicated IGLV3-21R110expressing cell lines and primary CLL cells, but not polyclonal healthy B cells. In vivo experiments confirmed epitope-selective cytolysis in xenograft models using engrafted IGLV3-21R110expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for novel avenues of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells.
Ribotin: Automated assembly and phasing of rDNA morphs
Authors: Rautiainen Mikko 
Published: October 2023

AbstractThe ribosomal DNA (rDNA) arrays are highly repetitive and homogenous regions which exist in all life. Due to their repetitiveness, current assembly methods do not fully assemble the rDNA arrays in humans and many other eukaryotes, and so variation within the rDNA arrays cannot be effectively studied. Here we present the tool ribotin to assemble full length rDNA copies, ormorphs. Ribotin uses a combination of highly accurate long reads and extremely long nanopore reads to resolve the variation between rDNA morphs. We show that ribotin successfully recovers the most abundant morphs in human and nonhuman genomes. We also find that genome wide consensus sequences of the rDNA arrays frequently produce a mosaic sequence that does not exist in the genome. Ribotin is available onhttps://github.com/maickrau/ribotinand as a package on bioconda.
Atomistic simulations of RNA duplex thermal denaturation: sequence- and forcefield-dependence
Authors: Dabin Aimeric , Stirnemann Guillaume 
Published: October 2023

AbstractDouble-stranded RNA is the end-product of template-based replication, and is also the functional state of some biological RNAs. Similarly to proteins and DNA, they can be denatured by temperature, with important physiological and technological implications. Here, we use anin silicostrategy to probe the thermal denaturation of RNA duplexes. Following previous results that were obtained on a few different duplexes, and which nuanced the canonical 2-state picture of nucleic acid denaturation, we here specifically address three different aspects that improve our description of the temperature-induced dsRNA separation. First, we investigate the effect of the spatial distribution of weak and strong base-pairs among the duplex sequence. We show that the deviations from the two-state dehybridization mechanism are more pronounced when a strong core is flanked with weak extremities, while duplexes with a weak core but strong extremities exhibit a two-state behavior, which can be explained by the key role played by base fraying. This was later verified by generating artificial hairpin or circular states containing one or two locked duplex extremities, which results in an important reinforcement of the entire HB structure of the duplex and higher melting temperatures. Finally, we demonstrate that our results are little sensitive to the employed combination of RNA and water forcefields. The trends in thermal stability among the different sequences as well as the observed unfolding mechanisms (and the deviations from a two-state scenario) remain the same regardless of the employed atomistic models. However, our study points to possible limitations of recent reparametrizations of the Amber RNA forcefield, which sometimes results in duplexes that readily denature under ambient conditions, in contradiction with available experimental results.
Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response
Authors: Lior Chen , Barki Debra , Iacobuzio-Donahue Christine A , Kelsen David , Scherz-Shouval Ruth 
Published: October 2023

AbstractThe tumor microenvironment (TME) is a challenging environment where cells must cope with stressful conditions such as fluctuating pH levels, hypoxia, and free radicals. In response, stress pathways are activated, which can both promote and inhibit tumorigenesis. In this study, we set out to characterize the stress response landscape across four carcinomas: breast, pancreas, ovary, and prostate tumors, focusing on five pathways: Heat shock response, oxidative stress response, unfolded protein response, hypoxia stress response, and DNA damage response. Using a combination of experimental and computational methods, we create an atlas of the stress response landscape across various types of carcinomas. We find that stress responses are heterogeneously activated in the TME, and highly activated near cancer cells. Focusing on the non-immune stroma we find, across tumor types, that NRF2 and the oxidative stress response are distinctly activated in immune-regulatory cancer-associated fibroblasts and in a unique subset of cancer associated pericytes. Our study thus provides an interactome of stress responses in cancer, offering new ways to intersect survival pathways within the tumor, and advance cancer therapy.
Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver Identifies Tissue- and Sex-Specific Changes with Implications for Genomic Imprinting
Authors: Morgan Rachel K. , Wang Kai , Svoboda Laurie K. , Rygiel Christine A. , Lalancette Claudia , Cavalcante Raymond , Bartolomei Marisa S. , Prasasya Rexxi , Neier Kari , Perera Bambarendage P.U. , Jones Tamara R , Colacino Justin A. , Sartor Maureen A. , Dolinoy Dana C. 
Published: October 2023

AbstractBackgroundMaternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications.ObjectiveWe examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2-ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver.MethodsFemale mice were exposed to human relevant doses of either Pb (32ppm) via drinking water or DEHP (5 mg/kg-day) via chow for two weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and Chipenrich were used for genomic annotations and geneset enrichment tests of DMRs, respectively.ResultsThe cortex contained the majority of DMRs associated with Pb (69%) and DEHP (58%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (n = 17 and 14 DMRs with Pb and DEHP exposure, respectively) and exposure types (n = 79 and 47 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5’ UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these,GnasandGrb10contained DMRs across tissues, sexes, and exposures. DMRs were enriched in the imprinting control regions (ICRs) ofGnasandGrb10, with 15 and 17 ICR-located DMRs across cortex, blood, and liver in each gene, respectively. The ICRs were also the location of DMRs replicated across target and surrogate tissues, suggesting epigenetic changes these regions may be potentially viable biomarkers.ConclusionsWe observed Pb- and DEHP-specific DNAm changes in cortex, blood, and liver, and the greatest degree of overlap in DMR signatures was seen between exposures followed by sex and tissue type. DNAm at imprinted control regions was altered by both Pb and DEHP, highlighting the susceptibility of genomic imprinting to these exposures during the perinatal window of development.
DASH-CAM: Dynamic Approximate SearcH Content Addressable Memory for genome classification
Authors: Jahshan Zuher , Merlin Itay , Garzón Esteban , Yavits Leonid 
Published: October 2023

ABSTRACTWe propose a novel dynamic storage-based approximate search content addressable memory (DASH-CAM) for computational genomics applications, particularly for identification and classification of viral pathogens of epidemic significance. DASH-CAM provides 5.5× better density compared to state-of-the-art SRAM-based approximate search CAM. This allows using DASH-CAM as a portable classifier that can be applied to pathogen surveillance in low-quality field settings during pandemics, as well as to pathogen diagnostics at points of care. DASH-CAM approximate search capabilities allow a high level of flexibility when dealing with a variety of industrial sequencers with different error profiles. DASH-CAM achieves up to 30% and 20% higherF1score when classifying DNA reads with 10% error rate, compared to state-of-the-art DNA classification tools MetaCache-GPU and Kraken2 respectively. Simulated at 1GHz, DASH-CAM provides 1, 178× and 1, 040× average speedup over MetaCache-GPU and Kraken2 respectively.CCS CONCEPTS•Hardware→Bio-embedded electronics.