bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can ChatGPT Aid Clinicians in Educating Patients on the Surgical Management of Glaucoma?
Authors: Kianian Reza , Sun Deyu , Giaconi JoAnn 
Published: November 2023

Précis:ChatGPT can help health care providers automate the quality assessment of online health information, but it does not produce easier-to-understand responses compared with existing online health information.Purpose:To compare the readability of ChatGPT-generated health information about glaucoma surgery to existing material online and to evaluate ChatGPT’s ability to analyze the quality of information found online about glaucoma surgery.Methods:ChatGPT was asked to create patient handouts on glaucoma surgery using 7 independent prompts, aiming to generate sixth grade level reading material. Existing patient-targeted online health information about glaucoma surgery was selected from the top 50 search results of 3 search engines, excluding advertisements, blog posts, information intended for health professionals, irrelevant content, and duplicate links. Four validated tools were used to assess readability, and the readability of the ChatGPT-generated material was compared with the readability of existing online information. The DISCERN instrument was used for the quality assessment of online materials. The DISCERN instrument was also programmed to use ChatGPT to evaluate its ability to analyze quality. R software and descriptive statistics were used for data analysis.Results:Thirty-five webpages were included. There was no difference between the reading level of online webpages (12th grade) and the reading level of ChatGPT-generated responses (11th grade), despite the ChatGPT prompts asking for simple language and a sixth grade reading level. The quality of health content was “fair,” with only 5 resources receiving an “excellent” score. ChatGPT scored the quality of health resources with high precision (r=0.725).Conclusions:Patient-targeted information on glaucoma surgery is beyond the reading level of the average patient, therefore at risk of not being understood, and is of subpar quality, per DISCERN tool scoring. ChatGPT did not generate documents at a lower reading level as prompted, but this tool can aid in automating the time-consuming and subjective process of quality assessment.
Informing Clinical Practice Guidelines for Children and Youth With Down Syndrome: A Survey of Key Partners
Authors: Wentz Erin , Conklin Ashley , Martin Kathy , Looper Julia , Shields Nora , Fiss Alyssa 
Published: November 2023

Purpose:The purpose of this work was to describe input from key partners to inform the scope and priorities for a clinical practice guideline (CPG) pertaining to physical therapy services provided to children and youth with Down syndrome (DS).Methods:A 68-item survey was completed by interventionists and parents (n = 296) of children and youth with DS.Results:The most prevalent physical therapy interventions currently being performed included tummy time, postural control activities, activity-based interventions, and play-based interventions. Key partners agreed on the importance of specific clinical outcomes, needing guidance on frequency and dosage of interventions, common barriers to physical therapy intervention, and needing information for discharge criteria in a future CPG.Conclusions:The results of this survey have given the CPG committee the necessary information to inform the CPG process for children and youth with DS.
Biofoundry-assisted Golden Gate cloning with AssemblyTron
Authors: Bryant John A. , Wright R. Clay 
Published: November 2023

AbstractGolden Gate assembly is a requisite method in synthetic biology that facilitates critical conventions such as genetic part abstraction and rapid prototyping. However, compared to robotic implementation, manual Golden Gate implementation is cumbersome, error-prone, and inconsistent for complex assembly designs. AssemblyTron is an open-source python package that provides an affordable automation solution using open-source Opentrons OT-2 lab robots. Automating Golden Gate assembly with AssemblyTron can reduce failure-rate, resource consumption, and training requirements for building complex DNA constructs, as well as indexed and combinatorial libraries. Here, we dissect a panel of upgrades to AssemblyTron’s Golden Gate assembly capabilities, which include Golden Gate assembly into modular cloning part vectors, error-prone PCR combinatorial mutant library assembly, and modular cloning indexed plasmid library assembly. These upgrades enable a broad pool of users with varying levels of experience to readily implement advanced Golden Gate applications using low-cost, open-source lab robotics.
Biomineralization and biomechanical trade-offs under heterogeneous environments in the eastern oysterCrassostrea virginica
Authors: Telesca Luca , Linsley Braddock K. , Witek Lukasz , Hönisch Bärbel 
Published: November 2023

ABSTRACTAccurate biological models are critical to reliably predict vulnerability of marine organisms and ecosystems to rapid environmental changes. Current predictions on the biological impacts of climate change and human-caused disturbances primarily stem from controlled experiments but lack assessments of the mechanisms underlying biotic variations in natural systems. Such information is key to translating experimental models to natural populations, especially for habitat-forming, climate sensitive species with key ecological roles. This study aimed to characterize and quantify spatial patterns of shell biomineralization and biomechanical properties in a key reef-building oyster,Crassostrea virginica, collected from restored reefs along natural estuarine gradients in the Hudson River Estuary (NY, U.S.). We characterized patterns of oyster shell production (i.e., shape and thickness), structure (i.e., abundance of foliated and chalky calcite), mineralogy (i.e., crystal size and density), composition (i.e., organic matrix and Mg/Ca ratios), and mechanical performance (i.e., elastic modulus and hardness) at the macro and micro scale. Our results demonstrate a strong protective capacity ofC. virginicafor compensatory adjustments in shell biomineralization and biomechanics to maintain shell production and protective functions as a response to biotic and abiotic stressors. We reveal salinity as a key predictor of oyster shell structure, mechanical integrity, and resistance to dissolution, and describe the functional role of chalky calcite in shaping shell mechanical performance. Compensatory adjustments along salinity gradients indicate that oysters produce shells withi) high mechanical resistance but increased vulnerability to dissolution under marine conditions, andii) lower structural integrity but higher protection from dissolution under brackish conditions. Our work illustrates that biomineralization and biomechanical adjustments may act as compensatory mechanisms in eastern oysters to maintain overall performance under heterogeneous estuarine environments, and could represent a cornerstone for calcifying organisms to acclimate and maintain their ecological functions in a rapidly changing climate.
Targeting with structural analogs of natural products the purine salvage pathway inLeishmania (Leishmania) infantumby computer-aided drug design approaches
Authors: Barazorda-Ccahuana Haruna Luz , Cárcamo-Rodriguez Eymi Gladys , Centeno-Lopez Angela Emperatriz , Galdino Alexsandro Sobreira , Machado-de-Ávila Ricardo Andrez , Giunchetti Rodolfo Cordeiro , Coelho Eduardo Antonio Ferraz , Chávez-Fumagalli Miguel Angel 
Published: November 2023

AbstractVisceral Leishmaniasis (VL) has a high death rate with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. To choose structural analogs from natural products that have demonstrated anti-leishmanial and anti-adenine phosphoribosyltransferase (APRT) properties, and that might bind with several targets from the purine salvage pathway, we used computer-aided drug design (CADD) techniques. Computational techniques were used to study the purine salvage pathway fromLeishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to twoL. infantumtargets, no expected toxicity, and potential for oral route administration. This study indicates that the compounds may have anti-leishmanial activity, which grantedin vitroandin vivoexperiments to settle this finding in the future.
Human dynein-dynactin is a fast processive motor in living cells
Authors: Verma Vikash , Wadsworth Patricia , Maresca Thomas J. 
Published: November 2023

ABSTRACTMinus-end directed transport along microtubules in eukaryotes is primarily mediated by cytoplasmic dynein and its cofactor dynactin. Significant advances have been made in recent years characterizing human dynein-dynactin structure and function using in vitro assays, however, there is limited knowledge about the motile properties and functional organization of dynein-dynactin in living human cells. Total internal reflection fluorescence microscopy (TIRFM) of CRISPR-engineered human cells is employed here to visualize fluorescently tagged dynein heavy chain (DHC) and p50 with high spatio-temporal resolution. We find that p50 and DHC exhibit indistinguishable motility properties in their velocities, run lengths, and run times. The dynein-dynactin complexes are fast (∼1.2 μm/s) and typically run for several microns (∼2.7 μm). Quantification of the fluorescence intensities of motile puncta reveals that dynein-dynactin runs are mediated by at least one DHC dimer while the velocity is consistent with that measured for double dynein (two DHC dimers) complexes in vitro.
Upper Bound on the Mutational Burden Imposed by a CRISPR-Cas9 Gene-Drive Element
Authors: Overton Michael S. , Guy Sean E. , Chen Xingsen , Martsul Alena , Carolino Krypton , Akbari Omar S. , Meyer Justin R. , Kryazhimskiy Sergey 
Published: November 2023

AbstractCRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To estimate how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeastSaccharomyces cerevisiae. Despite its substantial statistical power, our experiment revealed no detectable effect of CCGD or Cas9 alone on the genome-wide rates of mutations or LOH events, suggesting that these rates are affected by less than 30%. Nevertheless, we found that Cas9 caused a slight but significant shift towards more interstitial and fewer terminal LOH events, and the CCGD caused a significant difference in the distribution of LOH events on Chromosome V. Taken together, our results show that these genetic elements impose a weak and likely localized additional mutational burden in the yeast model. Although the mutagenic effects of CCGDs need to be further evaluated in other systems, our results suggest that the effect of CCGDs on off-target mutation rates and genetic diversity may be acceptable.
The applications of circulating cell-free DNA for oral squamous cell carcinoma patients as non-invasive diagnostics of structural variants, fusions and oncoviruses
Authors: Bhattacharya Mahua , Yaniv Dan , Yosefof Eyal , Tzelnick Sharon , Detroja Rajesh , D’Souza Dylan P. , Baum Gidi , Mizrachi Aviram , Bachar Gideon , Morgenstern Milana Frenkel 
Published: November 2023

AbstractCirculating cell-free DNA (cfDNA) has been widely used as a prognostic marker for different cancers. In this study, we used cfDNA from oral squamous cell carcinoma (OSCC) patients to study various correlation factors that could improve the disease early-stage diagnostics and/or prognosis. We found that OSCC patient cfDNA concentration can serve as an indicator of tumor stage, malignancy, and survival prognosis. Deep genome sequencing of cfDNA revealed genomic alterations, such as copy number variations, fusion gene identification, and viral integrations. Copy number variation analysis suggested correlation with amplification and deletion in chromosome 1 at loci 1q, 2q, 3p, 3q and 8q22. Moreover, at these loci, amplification ofTP53, PIK3CAand other genes related to keratinization in OSCC patients were observed. In addition, we identified the novel fusion gene,TRMO-TRNT1 ‘chimera’,in seven high-grade tumor samples. The parental genes of this chimera,TRMOandTRNT1, are known to play roles in tRNA modification and DNA repair, respectively. Therefore, our study indicates that liquid biopsy may thus serve as a sensitive tool to study OSCC patient genomic alterations by exploring cfDNA circulating in the plasma, by means of an easy-to-use blood test. Finally, we detected integrations of human papilloma virus, simian virus, and enterovirus in the OSCC samples, that may point to the origins of OSCC.
Predictors of symptom trajectory in newly diagnosed ulcerative colitis: a 3-year follow-up cohort study
Authors: Van Den Houte Maaike , Guadagnoli Livia , Ohman Lena , Simren Magnus , Strid Hans , Van Oudenhove Lukas , Svedlund Jan 
Published: November 2023

AbstractIntroductionPsychological symptoms are associated with poorer ulcerative colitis (UC)-related outcomes. However, the majority of research to date is cross-sectional and longitudinal data is lacking. We aimed to identify patient subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life (HRQoL), and to disentangle the directionality of effects between GI symptom levels and levels of psychological distress.MethodsSelf-reported GI symptom severity, HRQoL, inflammatory biomarkers and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis (LCGA) was used to determine subgroups based on longitudinal trajectories of symptom severity (diarrhea, abdominal pain) and physical and mental HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and GI symptom severity.ResultsDifferent subgroups were found based on the evolution of diarrhea, abdominal pain, and physical and mental HRQoL over time. Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhea (p = 0.049) and abdominal pain (p = 0.009). Conversely, patients with lower initial levels of diarrhea (p < 0.001) and abdominal pain (p = 0.003) had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment (p = 0.017), suggesting a subgroup of patients for whom initial poor mental health was inflammation-driven. Cross-lagged structural equation models indicated that reductions in diarrhea and abdominal pain preceded reductions in psychological symptoms over time (β=0.75, p <.0001), but not vice versa.ConclusionsBaseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Thus, intervening on abdominal pain may help prevent or reduce future psychological distress.
Y and Mitochondrial Chromosomes in the Heterogeneous Stock Rat Population
Authors: Okamoto Faith , Chitre Apurva S , Sanches Thiago Missfeldt , Chen Denghui , Munro Daniel ,   NIDA Center for GWAS in Outbred Rats, Polesskaya Oksana , Palmer Abraham A 
Published: November 2023

AbstractGenome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial Chromosomes. We genotyped the Y and mitochondrial chromosomes in heterogeneous stock rats (Rattus norvegicus), which were created in 1984 by intercrossing eight inbred strains and have subsequently been maintained as an outbred population for 100 generations. As the Y and mitochondrial Chromosomes do not recombine, we determined which founder had contributed these chromosomes for each rat, and then performed association analysis for all complex traits (n=12,055; intersection of 12,116 phenotyped and 15,042 haplotyped rats).We found the eight founders had 8 distinct Y and 4 distinct mitochondrial Chromosomes, however only two of each were observed in our modern heterogeneous stock rat population (Generations 81-97). Despite the unusually large sample size, the p-value distribution did not deviate from expectations; there were no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and mitochondrial Chromosomes were strongly associated with expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern heterogeneous stock rats there are no Y and mitochondrial Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and mitochondrial Chromosomes that do not appear in modern heterogeneous stock rats, nor do they address effects that may exist in other rat populations, or in other species.Article SummaryHeterogeneous stock rats were created in 1984 by intercrossing eight inbred strains. This genetically and phenotypically diverse population has been used for numerous genetic studies. We developed a method (leveraging existing data) to identify the founder strain origin of Y and mitochondrial Chromosomes in modern heterogeneous stock rats. We examined effects of these chromosomes’ genotype on behavioral, physiological, and gene expression traits among 12,055 rats. We found no significant associations, except for expression of genes located on these chromosomes.
DDX3X and DDX3Y constitutively form nano-sized RNA-protein clusters that foster enzymatic activity
Authors: Yanas Amber , Shweta Him , Owens Michael C. , Liu Kathy Fange , Goldman Yale E. 
Published: November 2023

AbstractDEAD-box helicases, which are crucial for many aspects of RNA metabolism, often contain intrinsically disordered regions (IDRs), whose functions remain unclear. Using multiparameter confocal microscopy, we reveal that sex chromosome-encoded homologous RNA helicases, DDX3X and DDX3Y, form nano-sized RNA-protein clusters (RPCs) that foster their catalytic activitiesin vitroand in cells. The IDRs are critical for the formation of these RPCs. A thorough analysis of the catalytic cycle of DDX3X and DDX3Y by ensemble biochemistry and single molecule photon bursts in the confocal microscope showed that RNA release is a major step that differentiates the unwinding activities of DDX3X and DDX3Y. Our findings provide new insights that the nano-sized helicase RPCs may be the normal state of these helicases under non-stressed conditions that promote their RNA unwinding and act as nucleation points for liquid-liquid phase separation under stress. This mechanism may apply broadly among other members of the DEAD-box helicase family.
PrimPol variant V102A with altered primase and polymerase activities
Authors: Boldinova Elizaveta O. , Filina Yulia V. , Miftakhova Regina R. , Shamsutdinova Yana F. , Makarova A.V. 
Published: November 2023

AbstractPrimPol is a human DNA primase-polymerase which restarts DNA synthesis beyond DNA lesions and non-B DNA structures blocking replication. Disfunction of PrimPol in cells leads to slowing of DNA replication rates in mitochondria and nucleus, accumulation of chromosome aberrations, cell cycle delay, elevated sensitivity to DNA-damaging agents. PrimPol has been suggested to be associated with the development of ophthalmic diseases, elevated mitochondrial toxicity of antiviral drugs and increased cell resistance to chemotherapy. Here, we describe a rare missense PrimPol variant V102A with altered biochemical properties identified in patients suffering from ovarian and cervical cancer. The Val102Ala substitution dramatically reduced both the primase and DNA polymerase activities of PrimPol as well as specifically decreased its ability to incorporate ribonucleotides. We suggest that substitutions in this region would likely distort the active site and affect the catalytic activity of PrimPol.
Predicting future hospital antimicrobial resistance prevalence using machine learning
Authors: Vihta Karina-Doris , Pritchard Emma , Pouwels Koen B. , Hopkins Susan , Guy Rebecca L , Henderson Katherine , Chudasama Dimple , Hope Russell , Muller-Pebody Berit , Walker Ann Sarah , Clifton David , Eyre David W. 
Published: November 2023

AbstractObjectivesPredicting antimicrobial resistance (AMR), a top global health threat, nationwide at a hospital level could help target interventions. Using machine learning, we exploit historical AMR and antimicrobial usage to predict future AMR.MethodsAntimicrobial use and AMR prevalence in bloodstream infections in hospitals in England were obtained per hospital group (Trust) and financial year (FY, April-March) for 22 pathogen-antibiotic combinations (FY2016-2017-FY2021-2022). XGBoost model predictions were compared to previous value taken forwards, difference between the previous two years taken forwards and linear trend forecasting (LTF). XGBoost feature importances were calculated to aid interpretability.ResultsRelatively limited year-to-year variability in AMR prevalence within Trust-pathogen-antibiotic combinations meant previous value taken forwards achieved a low mean absolute error (MAE). XGBoost models performed similarly, while difference between the previous two years taken forwards and LTF were consistently worse. XGBoost considerably outperformed all other methods in Trusts with a larger change in AMR prevalence from FY2020-2021 (last training year) to FY2021-2022 (held-out test set). Feature importance values indicated that complex relationships were exploited for predictions.ConclusionYear-to-year resistance has generally changed little within Trust-pathogen-antibiotic combinations. In those with larger changes, XGBoost models could improve predictions, enabling informed decisions, efficient resource allocation, and targeted interventions.