bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical Review: Methodological Variables in Clinical and Laboratory Measurements of Fixation Disparity
Authors: Fogt Nick 
Published: July 2023

ABSTRACT

Significance
Fixation disparity is a small vergence error that does not disrupt fusion. Fixation disparity measures correlate with binocular symptoms. This paper covers methodological differences between clinical fixation disparity measurement devices, findings when objective and subjective fixation disparities are compared, and the potential impact of binocular capture on fixation disparity measurements.
Fixation disparity is a small vergence error that occurs in non-strabismic individuals and does not disrupt fusion. This paper reviews clinical fixation disparity variables and their clinical diagnostic value. Clinical devices that are used to measure these variables are described as are studies in which the output from these devices have been compared. Methodological differences between the devices such as the location of the fusional stimulus, the rate at which judgments of dichoptic alignment are made, and the strength of the accommodative stimulus are all considered. In addition, the paper covers theories of the neural origins of fixation disparity and control systems models incorporating fixation disparity. Studies in which objective fixation disparities (oculomotor portion of fixation disparity assessed with an eye tracker) and subjective fixation disparities (sensory portion of fixation disparity assessed psychophysically with dichoptic Nonius lines) have been compared are also examined, and consideration is given to why some investigators find differences in these measures while other investigators do not. The conclusion thus far is that there are likely complex interactions between vergence adaptation, accommodation, and the location of the fusional stimulus that lead to differences in objective and subjective fixation disparity measures. Finally, capture of the visual direction of monocular stimuli by adjacent fusional stimuli and the implications for fixation disparity measures are considered.
Impact Of Community Privilege On Access To Care Among Patients Following Complex Cancer Surgery
Authors: Munir Muhammad Musaab , Endo Yutaka , Alaimo Laura , Moazzam Zorays , Lima Henrique A , Woldesenbet Selamawit , Azap Lovette , Beane Joal , Kim Alex , Dillhoff Mary , Cloyd Jordan , Ejaz Aslam , Pawlik Timothy M. 
Published: July 2023

Objective:
We sought to define the impact of community privilege on variations in travel patterns and access to care at high-volume hospitals for complex surgical procedures.

Background:
With increased emphasis on centralization of high-risk surgery, social determinants of health (SDOH) play a critical role in preventing equitable access to care. Privilege is a right, benefit, advantage, or opportunity that positively impacts all SDOH.

Methods:
The California Office of State-wide Health Planning Database identified patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for a malignant diagnosis between 2012 and 2016 and was merged using ZIP codes with the Index of Concentration of Extremes, a validated metric of both spatial polarization and privilege obtained from the American Community Survey. Clustered multivariable regression was performed to assess the probability of undergoing care at a high-volume center, bypassing the nearest and high-volume center, and total real driving time and travel distance.

Results:
Among 25,070 patients who underwent a complex oncologic operation (ES: n=1,216, 4.9%; PN: n=13,247, 52.8%; PD: n=3,559, 14.2%; PR: n=7,048, 28.1%), 5,019 (20.0%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 4,994 (19.9%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). Median travel distance was 33.1 miles (interquartile range [IQR] 14.4–72.2) and travel time was 16.4 minutes (IQR 8.3–30.2). Roughly, three-quarters of patients (overall: 74.8%, ES: 35.0%; PN: 74.3%; PD: 75.2%; LR: 82.2%) sought surgical care at a high-volume center. On multivariable regression, patients residing in the least advantaged communities were less likely to undergo surgery at a high-volume hospital (overall: odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52–0.81). Of note, individuals in the least privileged areas had longer travel distances (28.5 miles, 95%CI 21.2-35.8) and times (10.4 m, 95%CI 7.6-13.1) to reach the destination facility, as well as over 70% greater odds of bypassing a high-volume hospital to undergo surgical care at a low-volume center (OR 1.74, 95% CI 1.29-2.34) versus individuals living in the highest privileged areas.

Conclusions and Relevance:
Privilege had a marked effect on access to complex oncologic surgical care at high-volume centers. This highlights the need to focus on privilege as a key social determinant of health that influences patient access to and utilization of healthcare resources.
Strategies for Improving the Performance of Prediction Models for Response to Immune Checkpoint Blockade Therapy in Cancer
Authors: Zeng Tiantian , Zhang Jason , Stromberg Arnold , Chen Jin , Wang Chi 
Published: July 2023

AbstractImmune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valuable to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning methods to predict patients’ response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is challenging to develop well-performed gene expression signatures. In this study, we used several published melanoma datasets and investigated approaches that can improve the construction of gene expression-based prediction models. We found that merging datasets from multiple studies and incorporating prior biological knowledge yielded prediction models with higher predictive accuracies. Our finding suggests that these two strategies are of high value to identify ICB response biomarkers in future studies.
An Exploratory Study of the Association Between Preoperative Pain Catastrophizing Scale Scores and Postoperative Pain Experience in Total Knee Arthroplasty
Authors: Gill Christopher , Giuliano Karen 
Published: July 2023

AbstractIntroductionOpiate misuse is increasingly common and can result from a single opiate exposure. High pain catastrophizing scores have been linked with greater reported pain and increased opiate use in outpatient studies, but this association has not previously been established in a perioperative setting.MethodsA quantitative, cross-sectional pilot study was conducted on 21 patients undergoing total knee arthroplasty surgery. Pain Catastrophizing Scale (PCS) scores and patients’ ASA Physical Status classifications were collected prior to surgery. Postoperative pain scores were measured using an 11-point numeric rating scale (NRS) and postoperative opiate consumption was measured using modified morphine equivalents (MMEs). Data were analyzed using Spearman rank correlation coefficients.ResultsSignificant correlations were found between NRS pain scores at 6 hours post-surgery and 48 hours post-surgery (.455); and NRS pain scores at 6 hours post-surgery and opiate consumption within the first 24 hours post-surgery (.591). A significant correlation was also found between ASA Physical Status classification and total opiate consumption (.522). While rumination scores within the Pain Catastrophizing Scale were also moderately positively correlated with reported pain scores 12 hours post-surgery (.41) and morphine dosing at 48 hours (.40), they were not significant.ConclusionsEarly preemptive pain management is an important component of overall postoperative pain management and to reduce opiate use. Results support that the ASA Physical Status classification scores may be helpful in identifying patients at risk for high opiate use. For the PCS, more data are needed to determine the clinical usefulness of the PCS as an adjunct to overall postoperative pain management.
Later-life Mortality and the Repeal of Federal Prohibition
Authors: Jacks David S. , Pendakur Krishna , Shigeoka Hitoshi , Wray Anthony 
Published: July 2023

AbstractDespite a recent and dramatic re-evaluation of the health consequences of alcohol consumption, very little is known about the effects of in utero exposure to alcohol on long-run outcomes such as later-life mortality. Here, we investigate how state by year variation in alcohol control arising from the repeal of federal prohibition affects mortality for cohorts born in the 1930s. We find that individuals born in wet states experienced higher later-life mortality than individuals born in dry states, translating into a 3.3% increase in mortality rates between 1990 and 2004 for affected cohorts.
OncoCTMiner: streamlining precision oncology trial matching via molecular profile analysis
Authors: Xu Quan , Liu Yueyue , Sun Dawei , Huang Xiaoqian , Li Feihong , Zhai JinCheng , Li Yang , Zhou Qiming , Niu Beifang 
Published: July 2023

AbstractSummaryOncoCTMiner is an innovative platform that streamlines precision oncology trial matching by integrating genetic profile analysis and clinical data. It utilizes manual tagging and automated entity recognition to identify six major biomedical concepts within clinical trial records. The platform currently contains a database of over 457,000 clinical trials, enabling quick and advanced search functionalities. Additionally, OncoCTMiner features an automated matching system based on genetic profiles and clinical data, providing real-time matching reports for suitable clinical trials. This platform aims to enhance patient enrollment in precision oncology trials, facilitating the development of personalized cancer therapies.Availability and ImplementationOncoCTMiner is available athttps://oncoctminer.chosenmedinfo.com.Contactniubf@cnic.cnorqimingzhou@chosenmedtech.comSupplementary informationSupplementary data are available atmedRxivonline.Graphic AbstractGraphic abstract:A) OncoCTMiner’s role in precision oncology trial enrollment. B) OncoCTMiner takes clinical and genetic profiles as inputs and utilizes a trial matching and filtering system to generate a report of matched trials. C) Strategy for building the clinical trial eligibility criteria database. D) Automatic matching strategy for genomics-driven oncology trials.
Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling
Authors: Biswas Saptarshi , Shahriar Sanjid , Bachay Galina , Arvanitis Panos , Jamoul Danny , Brunken William J. , Agalliu Dritan 
Published: July 2023

SUMMARYInteractions among neuronal, glial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunction precedes vascular abnormalities in many retinal pathologies, how neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Usingin vivogenetic studies in mice, single-cell RNA-sequencing and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed inVglut1-/-retinas where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated inGnat1-/-retinas where constitutively depolarized rods release excessive glutamate. Norrin expression and endothelial Norrin/β-catenin signaling are downregulated inVglut1-/-retinas, and upregulated inGnat1-/-retinas. Pharmacological activation of endothelial Norrin/β-catenin signaling inVglut1-/-retinas rescued defects in deep plexus angiogenesis and paracellular BRB maturation. Our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating endothelial Norrin/β-catenin signaling.
Polygenic architecture of flowering time and its relationship with local environments in the grassBrachypodium distachyon
Authors: Minadakis Nikolaos , Kaderli Lars , Horvath Robert , Bourgeois Yann , Xu Wenbo , Thieme Michael , Woods Daniel P. , Roulin Anne C. 
Published: July 2023

AbstractSynchronizing the timing of reproduction with the environment is crucial in the wild. Among the multiple mechanisms annual plants evolved to sense their environment, the requirement of cold-mediated vernalization is a major process that prevents individuals from flowering during winter. In many annual plants including crops, both a long and short vernalization requirement can be observed within species, resulting in so-called early-(spring) and late (winter)-flowering genotypes. Here, using the grass modelBrachypodium distachyon, we explored the link between flowering time-related trait (vernalization requirement and flowering time), environmental variation, and diversity at flowering-time genes by combining measurements under greenhouse and outdoor conditions. These experiments confirmed thatB. distachyonnatural accessions display large differences regarding vernalization requirements and ultimately flowering time. We underline significant, albeit quantitative effects of current environmental conditions on flowering time-related traits. While disentangling the confounding effects of population structure on flowering time-related traits remains challenging, population genomics analyses indicate that well-characterized flowering-time genes may contribute significantly to flowering time variation and display signs of polygenic selection. Flowering-time genes, however, do not colocalize with GWAs peaks obtained with outdoor measurements, suggesting that additional genetic factors contribute to flowering time variation in the wild. Altogether, our study fosters our understanding of the polygenic architecture of flowering time in a natural grass system and opens new avenues of research to investigate the gene-by-environment interaction at play for this trait.Article SummarySynchronizing the timing of reproduction with the environment is crucial in the wild. We used here the modelBrachypodium distachyonto expand our knowledge on the adaptive potential and polygenic architecture of flowering time in wild grasses. While genetic factors play an important role in flowering time variation in our species, we showed that flowering time correlates with environmental variables and is therefore a locally adapted trait.
A flexible high-throughput cultivation protocol to assess the response of individuals’ gut microbiota to diet-, drug-, and host-related factors
Authors: Zünd Janina N. , Plüss Serafina , Mujezinovic Denisa , Menzi Carmen , von Bieberstein Philipp R. , de Wouters Tomas , Lacroix Christophe , Leventhal Gabriel E. , Pugin Benoit 
Published: July 2023

SUMMARYAnaerobic cultivation of fecal microbiota is a promising approach to investigate how gut microbial communities respond to specific intestinal conditions and perturbations. Here, we describe a practical protocol using 96-deepwell plates to cultivate stool-derived gut microbiota. Our protocol addresses key challenges in high-throughput culturing, including a thorough assessment of the impact of gas phase on medium chemistry, a modular medium preparation process to enable testing of several conditions in parallel, a medium formulation designed to maximize the compositional similarity of fecal cultures with the donor microbiota, and the creation of a step-by-step protocol detailing all practical procedures from material preparation to sample handling for analyses. Finally, we validated the protocol by demonstrating that cultivated fecal microbiota responded similarly to dietary fibers (resistant dextrin, soluble starch) and drugs (ciprofloxacin, 5-fluorouracil) as reported in vivo. This high-throughput cultivation protocol can facilitate culture-dependent studies, accelerate the discovery of gut microbiota-diet-drug-host interactions, and pave the way to personalized and microbiota-centered interventions.MOTIVATIONThe human gut microbiota is a complex ecosystem unique to each individual. The extent of this diversity has limited our capacity to fully comprehend microbial dynamics that apply to the entire human population. To probe the response of donor-specific microbial communities to intestinal conditions or perturbations,in vitrocultivation of stool-derived gut microbiota can be employed. However, cultivating gut microbiota under strictly anaerobic conditions is commonly performed using individual gas-tight tubes, which is a highly time-consuming strategy that limits the number of conditions and donor microbiota that can be tested in parallel. A flexible high-throughput protocol to cultivate and test donor-specific gut microbiota is therefore required. Hence, we developed a robust procedure for cultivating stool-derived microbiota (and pure gut microbial cultures) in 96-deepwell plates within an anaerobic chamber.
Amyloid β induces cardiac dysfunction and neuro-signaling impairment in the heart of an Alzheimer’s disease model
Authors: Elia Andrea , Parodi-Rullan Rebecca , Vazquez-Torres Rafael , Carey Ashley , Javadov Sabzali , Fossati Silvia 
Published: July 2023

AbstractAims:Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cerebral amyloid β (Aβ) deposition and tau pathology. The AD-mediated degeneration of the brain neuro-signaling pathways, together with a potential peripheral amyloid accumulation, may also result in the derangement of the peripheral nervous system, culminating in detrimental effects on other organs, including the heart. However, whether and how AD pathology modulates cardiac function, neurotrophins, innervation, and amyloidosis is still unknown. Here, we report for the first time that cardiac remodeling, amyloid deposition, and neuro-signaling dysregulation occur in the heart of Tg2576 mice, a widely used model of AD and cerebral amyloidosis.Methods and Results:Echocardiographic analysis showed significant deterioration of left ventricle function, evidenced by a decline of both ejection fraction and fraction shortening percentage in 12-month-old Tg2576 mice compared to age-matched WT littermates. Tg2576 mice hearts exhibited an accumulation of amyloid aggregates, including Aβ, an increase in interstitial fibrosis and severe cardiac nervous system dysfunction. The transgenic mice also showed a significant decrease in cardiac nerve fiber density, including both adrenergic and regenerating nerve endings. This myocardial denervation was accompanied by a robust reduction in NGF and BDNF protein expression as well as GAP-43 expression (regenerating fibers) in both the brain and heart of Tg2576 mice. Accordingly, cardiomyocytes and neuronal cells challenged with Aβ oligomers showed significant downregulation of BDNF and GAP-43, indicating a causal effect of Aβ on the loss of cardiac neurotrophic function.Conclusions:Overall, this study uncovers possible harmful effects of AD on the heart, revealing cardiac degeneration induced by Aβ through fibrosis and neuro-signaling pathway deregulation for the first time in Tg2576 mice. Our data suggest that AD pathology can cause deleterious effects on the heart, and the peripheral neurotrophic pathway may represent a potential therapeutic target to limit these effects.
Magnetic susceptibility is predictive of future clinical severity in Parkinson’s disease
Authors: Thomas George EC , Hannaway Naomi , Zarkali Angelika , Shmueli Karin , Weil Rimona S 
Published: July 2023

AbstractDementia is common in Parkinson’s disease, but there is wide variation in its timing. With the emergence of disease modifying treatments in neurodegeneration, there is increasing need to detect and treat disease at the earliest stages and to monitor disease progression. A critical gap in Parkinson’s disease is the lack of quantifiable markers of progression, and methods to identify early stages. Until recently, MRI has had limited sensitivity to detect or track changes relating to Parkinson’s dementia, but advanced techniques, especially quantitative magnetic susceptibility mapping (QSM) which is sensitive to brain tissue iron, show potential for these purposes. So far, QSM, applied to cognition in Parkinson’s, has only been investigated in detail in cross-sectional cohorts. Here we present a longitudinal study throughout the brain using QSM in Parkinson’s disease. We included 59 Parkinson’s patients (with no dementia at study onset), and 22 controls, at baseline and after 3-year follow-up. Participants underwent detailed assessments of motor and cognitive severity at both timepoints. We found that increased magnetic susceptibility values in right temporal cortex and right putamen in patients were associated with poorer cognition at baseline. Strikingly, increased baseline susceptibility values within right temporal cortex, nucleus basalis of Meynert and putamen in patients were associated with greater cognitive severity after 3-year follow-up; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex and dentate nucleus in patients were associated with greater motor severity after 3-year follow-up. We further found that after 3-years, increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, region of interest analyses revealed that, in cortical regions, increases in paramagnetic susceptibility relating to iron could not alone explain the associations with increased clinical severity that were observed; and, similar to other studies, we did not find consistent increases in susceptibility within the 3-year follow-up period. Our study suggests that QSM has predictive sensitivity to detect changes in clinical severity many months prior to overt cognitive involvement in Parkinson’s. However, it also suggests that susceptibility within brain tissue over time may relate to changes in tissue composition other than iron concentration, such as in the relative proportion of myelin. Whilst our findings open the door for QSM to detect patients at the earliest stages of Parkinson’s dementia, we will require additional tissue metrics to augment the interpretation QSM, such that it can be used robustly in clinical practice or to provide outcome measures in therapeutic trials for disease modifying treatments in neurodegeneration.