bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological Symptom Trajectories and Non–Small Cell Lung Cancer Survival: A Joint Model Analysis
Authors: Andersen Barbara L. , McElroy Joseph P. , Carbone David P. , Presley Carolyn J. , Smith Rachel M. , Shields Peter G. , Brock Guy N. 
Published: October 2021

ABSTRACT

Objective
Lung cancer remains the number one cause of cancer-related mortality worldwide, but less known is that lung cancer patients are among the most psychologically disabled of all cancer groups. Patients with stage IV non–small cell lung cancer (NSCLC) were studied to test the hypothesis that trajectories of depression and/or anxiety symptoms after diagnosis would show an adverse relationship with survival, beyond relevant controls.

Methods
Patients with stage IV NSCLC (n = 157) were enrolled (ClinicalTrials.gov Identifier: NCT03199651) at diagnosis and completed validated measures for depressive symptoms (Patient Health Questionnaire-9) and anxiety symptoms (Generalized Anxiety Disorder-7). Patients were reassessed every 1 to 2 months through 24 months (16 assessments; 80% average completion rate) and survival monitored. Joint statistical models provided simultaneous modeling of longitudinal (psychological) and time-to-event (survival) processes. Control variables were age, sex, marital status, education, smoking status, cancer type, and treatment received.

Results
Depression and anxiety symptoms significantly decreased with time since diagnosis. The 2-year trajectory of depressive symptoms was significantly associated with cancer survival after adjustment for covariates (hazard ratio = 1.09 per unit increase in the Patient Health Questionnaire-9, 95% confidence interval = 1.03–1.15, p = .002). Anxiety was marginally significant in the unadjusted (p = .053) but not the adjusted (p = .39) model.

Conclusions
For the first time, joint model analyses test the interaction of a longitudinal trajectory of psychological symptoms, assessed from diagnosis to 24 months, and cancer survival. New data show the continuation of depressive and anxiety symptoms through treatment and thereafter. Immunotherapy and targeted therapies have dramatically improved survival for patients with advanced NSCLC; however, novel data suggest their benefit may be constrained by depressive symptoms.
Solitary Isolated Dural Metastasis From Lung Adenocarcinoma Mimicking Meningioma
Authors: Zhang Jun , Dong Aisheng , Wang Yang 
Published: October 2021

Abstract
Solitary isolated dural metastasis is extremely rare. Distinguishing solitary dural metastasis from meningioma based on radiological findings can be challenging. We describe MRI and FDG PET/CT findings in 2 cases of histologically proved solitary isolated dural metastasis from lung adenocarcinoma. Enhanced brain MRI of the 2 cases showed parafalcine extra-axial, dural-based tumors with hypervascularity mimicking meningioma. Preoperative FDG PET/CT was performed in one case with a known history of lung adenocarcinoma showing intense FDG uptake of the parafalcine tumor. Postoperative FDG PET/CT was performed in the other case showing solitary lung tumor, suggestive of the primary tumor.
UAMC-3203 or/and Deferoxamine Improve Post-Resuscitation Myocardial Dysfunction Through Suppressing Ferroptosis in a Rat Model of Cardiac Arrest
Authors: Jin Tao , He Qing , Cheng Cheng , Li Hui , Liang Lian , Zhang Guozhen , Su Chenglei , Xiao Yan , Bradley Jennifer , Peberdy Mary Ann , Ornato Joseph P. , Tang Wanchun 
Published: October 2021

ABSTRACT
Blocking ferroptosis reduces ischemia-reperfusion injury in some pathological contexts. However, there is no evidence that ferroptosis contributes to post-resuscitation myocardial dysfunction (PRMD). Here, we evaluated the therapeutic performance of ferroptosis inhibitors (UAMC-3203 or/and Deferoxamine) on the PRMD in a rat model of cardiac arrest and surveyed the changes of essential ferroptosis markers in the myocardium. Remarkably, all treatments reduce the severity of cardiac dysfunction and microcirculation hypoperfusion after resuscitation compared with control. Consistently, we observe that the ferroptosis marker Glutathione peroxidase 4, 4-hydroxynonenal and non-heme iron altered (1 ± 0.060 vs. 0.021 ± 0.016, 1 ± 0.145 vs. 3.338 ± 0.221, 52.010 ± 3.587 ug/g vs. 70.500 ± 3.158 ug/g, all P < 0.05) in the myocardium after resuscitation. These changes were significantly suppressed by UAMC-3203 [(0.187 ± 0.043, 2.848 ± 0.169, all P < 0.05), (72.43 ± 4.920 ug/g, P
> 0.05)], or Deferoxamine (0.203 ± 0.025, 2.683 ± 0.273, 55.95 ± 2.497 ug/g, all P < 0.05). Briefly, UAMC-3203 or/and Deferoxamine improve post-resuscitation myocardial dysfunction and provide evidence of ferroptosis involvement, suggesting that ferroptosis inhibitors could potentially provide an innovative therapeutic approach for mitigating the myocardial damage caused by cardiopulmonary resuscitation.
Association of County-level Upward Economic Mobility with Stage at Diagnosis and Receipt of Treatment Among Patients Diagnosed with Pancreatic Adenocarcinoma
Authors: Dalmacy Djhenne , Paro Alessandro , Hyer J. Madison , Obeng-Gyasi Samilia , Pawlik Timothy M. 
Published: October 2021

Objective:
Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma.

Summary background data:
The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown.

Methods:
Pancreatic adenocarcinoma patients diagnosed in 2004–2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity.

Results:
Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07–1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41–1.77) or chemotherapy (OR 1.51, 95% CI 1.39–1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02–1.22 and OR 1.35, 95% CI 1.02–1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59–1.88 and OR 1.49, 95% CI 1.13–1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96–1.71 and OR 1.30, 95% CI 0.99–1.72, respectively).

Conclusions:
Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients.
The Use of Learning Analytics to Enable Detection of Underperforming Trainees
Authors: Smith Brigitte K. , Yamazaki Kenji , Tekian Ara , Holmboe Eric , Hamstra Stanley J. , Mitchell Erica L. , Park Yoon Soo 
Published: October 2021

Objective:
This study aims to investigate at-risk scores of semiannual Accreditation Council for Graduate Medical Education (ACGME) Milestone ratings for vascular surgical trainees' final achievement of competency targets.

Summary Background Data:
ACGME Milestones assessments have been collected since 2015 for Vascular Surgery. It is unclear whether milestone ratings throughout training predict achievement of recommended performance targets upon graduation.

Methods:
National ACGME Milestones data were utilized for analyses. All trainees completing 2-year vascular surgery fellowships in June 2018 and 5-year integrated vascular surgery residencies in June 2019 were included. A generalized estimating equations model was used to obtain at-risk scores for each of the 31 subcompetencies by semiannual review periods, to estimate the probability of trainees achieving the recommended graduation target based on their previous ratings.

Results:
A total of 122 vascular surgery fellows (VSFs) (95.3%) and 52 integrated vascular surgery residents (IVSRs) (100%) were included. VSFs and IVSRs did not achieve level 4.0 competency targets at a rate of 1.6% to 25.4% across subcompetencies, which was not significantly different between the 2 groups for any of the subcompetencies (P = 0.161–0.999). Trainees were found to be at greater risk of not achieving competency targets when lower milestone ratings were assigned, and at later time-points in training. At a milestone rating of 2.5, with 1 year remaining before graduation, the at-risk score for not achieving the target level 4.0 milestone ranged from 2.9% to 77.9% for VSFs and 33.3% to 75.0% for IVSRs.

Conclusion:
The ACGME Milestones provide early diagnostic and predictive information for vascular surgery trainees' achievement of competence at completion of training.
Spinal cord pathology revealed by MRI in traumatic spinal cord injury
Authors: Pfyffer Dario , Freund Patrick 
Published: October 2021

Purpose of review
This review covers recent advances in identifying conventional and quantitative neuroimaging spinal cord biomarkers of lesion severity and remote spinal cord pathology following traumatic spinal cord injury (SCI). It discusses the potential of the most sensitive neuroimaging spinal cord biomarkers to complement clinical workup and improve prediction of recovery.

Recent findings
At the injury site, preserved midsagittal tissue bridges – based on conventional sagittal T2-weighted scans – can be identified in the majority of SCI patients; its width being predictive of recovery. Remote from the injury, diffusion indices, and myelin/iron-sensitive neuroimaging-based changes are sensitive to secondary disease processes; its magnitude of change being associated with neurological outcome.

Summary
Neuroimaging biomarkers reveal focal and remote cord pathology. These biomarkers show sensitivity to the underlying disease processes and are clinically eloquent. Thus, they improve injury characterization, enable spatiotemporal tracking of cord pathology, and predict recovery of function following traumatic SCI. Neuroimaging biomarkers, therefore, hold potential to complement the clinical diagnostic workup, improve patient stratification, and can serve as potential endpoints in clinical trials.
Induced Pluripotent Stem Cells for Inherited Optic Neuropathies—Disease Modeling and Therapeutic Development
Authors: Harvey Joshua Paul , Sladen Paul Edward , Yu-Wai-Man Patrick , Cheetham Michael E. 
Published: October 2021

Background:
Inherited optic neuropathies (IONs) cause progressive irreversible visual loss in children and young adults. There are limited disease-modifying treatments, and most patients progress to become severely visually impaired, fulfilling the legal criteria for blind registration. The seminal discovery of the technique for reprogramming somatic nondividing cells into induced pluripotent stem cells (iPSCs) has opened several exciting opportunities in the field of ION research and treatment.

Evidence Acquisition:
A systematic review of the literature was conducted with PubMed using the following search terms: autosomal dominant optic atrophy, ADOA, dominant optic atrophy, DOA, Leber hereditary optic neuropathy, LHON, optic atrophy, induced pluripotent stem cell, iPSC, iPSC derived, iPS, stem cell, retinal ganglion cell, and RGC. Clinical trials were identified on the ClinicalTrials.gov website.

Results:
This review article is focused on disease modeling and the therapeutic strategies being explored with iPSC technologies for the 2 most common IONs, namely, dominant optic atrophy and Leber hereditary optic neuropathy. The rationale and translational advances for cell-based and gene-based therapies are explored, as well as opportunities for neuroprotection and drug screening.

Conclusions:
iPSCs offer an elegant, patient-focused solution to the investigation of the genetic defects and disease mechanisms underpinning IONs. Furthermore, this group of disorders is uniquely amenable to both the disease modeling capability and the therapeutic potential that iPSCs offer. This fast-moving area will remain at the forefront of both basic and translational ION research in the coming years, with the potential to accelerate the development of effective therapies for patients affected with these blinding diseases.
Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico
Authors: Dunkle Lisa M. , Kotloff Karen L. , Gay Cynthia L. , Áñez Germán , Adelglass Jeffrey M. , Barrat Hernández Alejandro Q. , Harper Wayne L. , Duncanson Daniel M. , McArthur Monica A. , Florescu Diana F. , McClelland R. Scott , Garcia-Fragoso Veronica , Riesenberg Robert A. , Musante David B. , Fried David L. , Safirstein Beth E. , McKenzie Mark , Jeanfreau Robert J. , Kingsley Jeffrey K. , Henderson Jeffrey A. , Lane Dakotah C. , Ruíz-Palacios Guillermo M. , Corey Lawrence , Neuzil Kathleen M. , Coombs Robert W. , Greninger Alex L. , Hutter Julia , Ake Julie A. , Smith Katherine , Woo Wayne , Cho Iksung , Glenn Gregory M. , Dubovsky Filip ,   for the 2019nCoV-301 Study Group
Published: October 2021

AbstractBACKGROUNDVaccination using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antigen has been effective in the prevention of coronavirus disease 2019 (Covid-19). NVX-CoV2373 is an adjuvanted, recombinant S protein nanoparticle vaccine that demonstrated clinical efficacy for prevention of Covid-19 in phase 2b/3 trials in the United Kingdom and South Africa.METHODSThis phase 3, randomized, observer-blinded, placebo-controlled trial evaluated the efficacy and safety of NVX-CoV2373 in adults ≥18 years of age in the United States and Mexico during the first quarter of 2021. Participants were randomized in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary end point was vaccine efficacy (VE) against reverse transcriptase-polymerase chain reaction-confirmed Covid-19 in SARS-CoV-2-naïve participants ≥7 days after the second dose administration.RESULTSOf the 29,949 participants randomized between December 27, 2020, and February 18, 2021, 29,582 (median age: 47 years, 12.6% ≥65 years) received ≥1 dose: 19,714 received vaccine and 9868 placebo. In the per-protocol population, there were 77 Covid-19 cases; 14 among vaccine and 63 among placebo recipients (VE: 90.4%, 95% confidence interval [CI] 82.9 to 94.6, P<0.001). All moderate-to-severe cases occurred in placebo recipients, yielding VE of 100% (95% CI 87.0 to 100). Most sequenced viral genomes (48/61, 78.7%) were variants of concern (VOC) or interest (VOI), mainly represented by variant alpha/B.1.1.7 (31/35, 88.6% VOC identified). VE against any VOC/VOI was 92.6% (95% CI 83.6 to 96.7). Reactogenicity was mostly mild-to-moderate and transient, but more frequent in NVX-CoV2373 recipients and after the second dose. Serious adverse events were rare and evenly distributed between treatments.CONCLUSIONSNVX-CoV2373 was well tolerated and demonstrated a high overall VE (>90%) for prevention of Covid-19, with most cases due to variant strains.(Funded by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health; PREVENT-19 ClinicalTrials.gov number, NCT04611802.)
The influence of reproductive stage on cerebellar network connectivity across adulthood
Authors: Ballard Hannah K. , Jackson T. Bryan , Hicks Tracey H. , Bernard Jessica A. 
Published: October 2021

AbstractSex-specific differences in the aging cerebellum may be related to hormone changes with menopause. We evaluated the influence of reproductive stage on lobular cerebellar network connectivity using data from the Cambridge Centre for Ageing and Neuroscience repository. We used raw structural and resting state neuroimaging data and information regarding age, sex, and menopause-related variables. Crus I and II and Lobules V and VI were our cerebellar seeds of interest. We characterized reproductive stage using the Stages of Reproductive Aging Workshop criteria. Results show that postmenopausal females have lower cerebello-striatal and cerebello-cortical connectivity, particularly in frontal regions, along with lower connectivity within the cerebellum, compared to reproductive females. Postmenopausal females also exhibit greater connectivity in some brain areas as well. Differences begin to emerge across transitional stages of menopause. Further, results reveal sex-specific differences in connectivity between female reproductive groups and age-matched male control groups. This suggests that menopause may influence cerebellar network connectivity in aging females, and sex differences in the aging brain may be related to this biological process.HighlightsLobular analysis of cerebellar network connectivity across reproductive stagesPostmenopausal females show lower cerebellar connectivity, compared to reproductiveConnectivity differences begin to emerge in transitional stages of menopauseAge-matched male control groups show distinct patterns of cerebellar connectivityReproductive stage influences cerebellar network connectivity in aging females
Use of a graph neural network to the weighted gene co-expression network analysis of Korean native cattle
Authors: Lee Hyo-Jun , Chung Yoonji , Chung Ki Yong , Kim Young-Kuk , Lee Jun Heon , Koh Yeong Jun , Lee Seung Hwan 
Published: October 2021

AbstractIn the general framework of the weighted gene co-expression network analysis (WGCNA), a hierarchical clustering algorithm is commonly used to module definition. However, hierarchical clustering depends strongly on the topological overlap measure. In other words, this algorithm may assign two genes with low topological overlap to different modules even though their expression patterns are similar. Here, a novel gene module clustering algorithm for WGCNA is proposed. We develop a gene module clustering network (gmcNet), which simultaneously addresses single-level expression and topological overlap measure. The proposed gmcNet includes a “co-expression pattern recognizer” (CEPR) and “module classifier”. The CEPR incorporates expression features of single genes into the topological features of co-expressed ones. Given this CEPR-embedded feature, the module classifier computes module assignment probabilities. We validated gmcNet performance using 4,976 genes from 20 native Korean cattle. We observed that the CEPR generates more robust features than single-level expression or topological overlap measure. Given the CEPR-embedded feature, gmcNet achieved the best performance in terms of modularity (0.261) and the differentially expressed signal (27.739) compared with other clustering methods tested. Furthermore, gmcNet detected some interesting biological functionalities for carcass weight, backfat thickness, intramuscular fat, and beef tenderness of Korean native cattle. Therefore, gmcNet is a useful framework for WGCNA module clustering.Author summaryA graph neural network is a good alternative algorithm for WGCNA module clustering. Even though the graph-based learning methods have been widely applied in bioinformatics, most studies on WGCNA did not use graph neural network for module clustering. In addition, existing methods depend on topological overlap measure of gene pairs. This can degrade similarity of expression not only between modules, but also within module. On the other hand, the proposed gmcNet, which works similar to message-passing operation of graph neural network, simultaneously addresses single-level expression and topological overlap measure. We observed the higher performance of gmcNet comparing to existing methods for WGCNA module clustering. To adopt gmcNet as clustering algorithm of WGCNA, it remains future research issues to add noise filtering and optimal k search on gmcNet. This further research will extend our proposed method to be a useful module clustering algorithm in WGCNA. Furthermore, our findings will be of interest to computational biologists since the studies using graph neural networks to WGCNA are still rare.
Reservoir host immunology and life history shape virulence evolution in zoonotic viruses
Authors: Brook Cara E. , Rozins Carly , Guth Sarah , Boots Mike 
Published: October 2021

AbstractThe management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms which underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, successfully recapturing corresponding virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic explanation for the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and hypotheses designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts.
No difference in retinal fluorescence after oral curcumin intake in amyloid proven AD cases compared to controls
Authors: den Haan Jurre , Hart de Ruyter Frederique J. , Lochocki Benjamin , Kroon Maurice A.G.M. , Kemper E. Marleen , Teunissen Charlotte E. , van Berckel Bart , Scheltens Philip , Hoozemans Jeroen J. , van de Kreeke Aleid , Verbraak Frank D. , de Boer Johannes F. , Bouwman Femke H. 
Published: October 2021

AbstractINTRODUCTIONPrevious work showed thein-vivopresence of retinal amyloid in AD patients using curcumin. We aimed to replicate these findings in an amyloid biomarker confirmed cohort.METHODSTwenty-six AD patients (age 66 (+9), MMSE≥17) and 14 controls (age 71(+12)) used one of three curcumin formulations: Longvida®, Theracurmin®and Novasol®.Plasma levels were determined and pre- and post-curcumin retinal fluorescence scans were visually assessed in all cases and quantitatively assessed in a subset.RESULTSVisual assessment showed no difference between AD patients and controls for pre- and post-curcumin images. This was confirmed by quantitative analyses on a subset. Mean conjugated plasma curcumin levels were 198.7 nM (Longvida®), 576.6 nM (Theracurmin®) and 1605.8 nM (Novasol®).DISCUSSIONWe found no difference in retinal fluorescence betweenamyloid confirmed AD cases and control participants, using Longvida®and two additional curcumin formulations. Additional replication studies in amyloid confirmed cohorts are needed to assess the diagnostic value of retinal fluorescence as an AD biomarker.