tbuckley/cabot-search huggingface dataset:
18F-Choline PET Detected the Third Ventricle Craniopharyngioma
Authors: Yunqi Zhu, Kui Zhao, Zhen Wang, Yafei Zhang, Xiaoya Lu
Journal: Clinical Nuclear Medicine (2021)

Abstract Craniopharyngiomas are rare tumors of low histological malignancy (World Health Organization grade I) in the sellar and suprasellar region of the brain. We report a case of the third ventricular craniopharyngioma detected using 18 F-choline PET/CT in a 43-year-old man. MRI of the brain revealed an intense gadolinium enhancement focus in the same area. Histology revealed characteristics of papillary craniopharyngioma. Our findings suggest that craniopharyngioma should be included in the differential diagnosis of 18 F-choline–avid brain lesions.
Abstract 10546: Predictors of Changes in Peak Oxygen Consumption Following Outpatient Cardiac Rehabilitation: Importance of Cardiac Rehabilitation Adherence
Authors: Kasara A Little, Joshua R Smith, Jose Medina-inojosa, Audry Chacin Suarez, Jenna L Taylor, Shane Hammer, Karen Fischer, Amanda Bonikowske, Ray W Squires, Randal J Thomas, Thomas P Olson
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation (CR) is associated with improvements in exercise capacity (peak oxygen uptake (VO 2 peak)); however, 23% of CR patients do not improve VO 2 peak following CR. CR adherence (i.e. number of CR sessions attended) has been proposed to play an important role in VO 2 peak improvement following CR, but has not been investigated. Identifying clinical predictors of VO 2 peak improvement are critical as the degree of VO 2 peak improvement is associated with improved long-term outcomes in these patients. Purpose: To determine if clinical characteristics and number of CR sessions attended were predictive of patients who exhibited improvement in VO 2 peak following CR. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified all consecutive patients &gt;18 years old from Olmsted County, Minnesota who underwent cardiopulmonary exercise testing prior to and following CR from 1999 to 2017. Regression models were created to assess clinical predictors of VO 2 peak improvement (&gt;0% baseline) following CR. Results: The analysis included 804 patients (75% men) with a mean age of 60.7±12.4 years. Of the 804 patients, 609 (76%) patients exhibited VO 2 peak improvement following CR. Significant univariate predictors of VO 2 peak improvement included younger age (OR: 0.99, 95% CI: 0.97-1.00), lower pre-CR VO 2 peak (OR: 0.97, 95% CI: 0.94-0.99), history of peripheral artery disease (OR: 0.48, 95% CI: 0.32-0.73), and smoking (OR: 0.63, 95% CI: 0.45-0.90). Significant independent predictors of VO 2 peak improvement from a multivariate analysis included younger age (OR: 0.98, 95% CI: 0.96-1.00), number of CR sessions (OR: 1.02, 95% CI: 1.01-1.03), lower pre-CR VO 2 peak (OR: 0.94, 95% CI: 0.91-0.96), history of peripheral artery disease (OR: 0.42, 95% CI: 0.27-0.66), and smoking (OR: 0.56, 95% CI: 0.39-0.82). Conclusions: These findings demonstrate the importance of CR adherence and individual clinical characteristics in influencing VO 2 peak improvement following CR in patients with CVD. These findings may influence the clinical practice by providing specific clinical characteristics to account for when personalizing the CR treatment plan to maximize positive outcomes.
The “‘Crisis’ Crisis” in psychology
Authors: John D. Medaglia, Kiante A. Fernandez
Journal: Behavioral and Brain Sciences (2022)

The recent trend to label dilemmas in psychology as "crises" is insidious. The "'Crisis' Crisis" in psychology can distract us from actionable practices. As a case in point, "The Generalizability Crisis" offers the valuable central thesis that verbal-quantitative gaps imperil psychological science. Focusing on the key issues rather than crisis narratives can lead to progress in our discourse and research.
Locus-specific induction of gene expression from heterochromatin loci during cellular senescence
Authors: Kosuke Tomimatsu, Dóra Bihary, Ioana Olan, Aled J. Parry, Stefan Schoenfelder, Adelyne S. L. Chan, Guy St. C. Slater, Yoko Ito, Peter J. Rugg-Gunn, Kristina Kirschner, Camino Bermejo-Rodriguez, Tomomi Seko, Hiroyuki Kugoh, Ken Shiraishi, Koji Sayama, Hiroshi Kimura, Peter Fraser, Masako Narita, Shamith A. Samarajiwa, Masashi Narita
Journal: Nature Aging (2021)
Peritoneal Tuberculosis Mimicking Peritoneal Carcinomatosis on 68Ga-FAPI-04 and 18F-FDG PET/CT
Authors: Göksel Alçın, Gamze Tatar, Rahime Şahin, Mehmet Can Baloğlu, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2022)

We report a case of tuberculosis peritonitis in a 26-year-old woman who presented with abdominal pain, fatigue, and weight loss for the last 4 months. Abdominal US and CT demonstrated intra-abdominal massive ascites, misty mesentery, and diffuse peritoneal thickening. In addition, 3 nodular lesions were detected in the right lung. 18 F-FDG PET/CT showed hypermetabolism in lung nodules, mesenteric area, peritoneal thickening, and ascites. 68 Ga-FAPI-04 (fibroblast activation protein-specific inhibitor) PET/CT imaging was also performed; high uptakes were detected in the same regions of 18 F-FDG PET/CT. Tuberculosis diagnosis was made after histopathological examination of wedge resection of the right lung.
184P Early-stage diagnosis of lung cancer with liquid biopsy test based on peripheral blood cells
Authors: A.R. Thomsen, S. Ott, S. Vesenbeckh, N. Calatayud, Z. Barekati, O. Schicht, A. Faisst, F. Staedtler, J. Godau, B. Woelnerhanssen
Journal: Annals of Oncology (2022)
19P Stable disease (SD) on amivantamab in post-platinum epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutated non-small cell lung cancer (NSCLC): A response-based analysis
Authors: N. Girard, K. Park, S. Viteri, C.A. Schioppa, J. Diels, M. Oguz, B.H. Rodrigues, N. Rahhali, J. Sermon, F. Ghilotti, T. Li, R.E. Knoblauch, P. Mahadevia, B.C. Cho
Journal: Annals of Oncology (2022)
Effects of Inhaled Corticosteroid/Long-Acting β<sub>2</sub>-Agonist Combination on the Airway Microbiome of Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Clinical Trial (DISARM)
Authors: Fernando Sergio Leitao Filho, Hiroto Takiguchi, Kentaro Akata, Seung Won Ra, Ji-Yong Moon, Hyun Kuk Kim, Yuji Cho, Kei Yamasaki, Stephen Milne, Julia Yang, Cheng Wei Tony Yang, Xuan Li, Corey Nislow, Stephan F. van Eeden, Tawimas Shaipanich, Stephen Lam, Janice M. Leung, Don D. Sin
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in α-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov (NCT02833480).
Detection of Diffuse Peritoneal and Omental Metastases From Prostate Cancer With 18F-PSMA-1007 PET/CT
Authors: Xiaowei Ji, Ling Wang, Jie Lin, Kun Tang
Journal: Clinical Nuclear Medicine (2021)

Diffuse peritoneal and omental infiltration of prostate cancer detected by 18F-PSMA-1007 PET/CT was rarely reported. We report a case of an 80-year-old man who was suspected of prostate carcinoma metastasis and underwent 18F-PSMA-1007 PET/CT for restaging the disease. PET/CT imaging presented intense tracer uptake in the prostate gland, multiple lymph nodes, and bones. Interestingly, we found extremely increased radioactive uptake of diffuse peritoneum and omentum on 18F-PSMA-1007 PET/CT images, which are very rare metastatic sites for prostate cancer.
Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent, specific and orally active P-glycoprotein (P-gp) inhibitor
Authors: Sai-Qi Wang, Qiu-Xu Teng, Shuai Wang, Zi-Ning Lei, Hui-Hui Hu, Hui-Fang Lv, Bei-Bei Chen, Jian-Zheng Wang, Xiao-Jing Shi, Wei-Feng Xu, Hong-Min Liu, Xiao-Bing Chen, Zhe-Sheng Chen, Bin Yu
Journal: Acta Pharmaceutica Sinica B (2022)

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.
Response by Zhang and Wang to Letter Regarding Article, “Integrated Stress Response Couples Mitochondrial Protein Translation With Oxidative Stress Control”
Authors: Guangyu Zhang, Zhao V. Wang
Journal: Circulation (2022)

In Response:We appreciate the comments on our study of the integrated stress response (ISR) in ischemic heart disease. 1 The authors raise an important point regarding how cells balance the acute PERK (PKR-like endoplasmic reticulum resident kinase)/ISR activation that improves survival and chronic PERK/ISR elevation, which triggers cell death.We agree with the authors that chronic activation of the PERK axis of the ISR may induce apoptosis during cardiac ischemia/reperfusion (I/R).In our study, we found that PERK and its downstream pathway is mainly activated in the acute phase of reperfusion.This signaling disappears rapidly, especially in mouse hearts in vivo.We therefore focused on the acute action of the PERK axis of the ISR.We found that activation of PERK right before reperfusion or at the time of reperfusion protects the heart against I/R injury.The underlying mechanism may involve selective decreases of mitochondrial-derived reactive oxygen species.However, it remains to be determined how the transition from acute to chronic ISR occurs.A recent study may provide some insights. 2Kaspar et al 2 found that CHOP (C/EBP homologous protein), a downstream transcriptional factor of the ISR, plays a rheostat role that attenuates prolonged ISR and prevents unfavorable metabolic alterations under mitochondrial dysfunction.CHOP is required to adjust ATF4 (activating transcription factor 4) levels and keep the ATF4regulated transcriptional program under check.Failure of governance by CHOP triggers the transition from acute to chronic ISR.On the other hand, we recognize that CHOP deletion improves cardiac response under I/R, as shown by Miyazaki et al 3 using a whole-body CHOP deficiency mouse model.Future work is needed to determine whether CHOP plays a role in the transition of the ISR under cardiac I/R and whether cell
The double agents in liquid biopsy: promoter and informant biomarkers of early metastases in breast cancer
Authors: Vinitha Richard, Matthew G. Davey, Heidi Annuk, Nicola Miller, Michael J. Kerin
Journal: Molecular Cancer (2022)

Abstract Breast cancer continues to be a major global problem with significant mortality associated with advanced stage and metastases at clinical presentation. However, several findings suggest that metastasis is indeed an early occurrence. The standard diagnostic techniques such as invasive core needle biopsy, serological protein marker assays, and non-invasive radiological imaging do not provide information about the presence and molecular profile of small fractions of early metastatic tumor cells which are prematurely dispersed in the circulatory system. These circulating tumor cells (CTCs) diverge from the primary tumors as clusters with a defined secretome comprised of circulating cell-free nucleic acids and small microRNAs (miRNAs). These circulatory biomarkers provide a blueprint of the mutational profile of the tumor burden and tumor associated alterations in the molecular signaling pathways involved in oncogenesis. Amidst the multitude of circulatory biomarkers, miRNAs serve as relatively stable and precise biomarkers in the blood for the early detection of CTCs, and promote step-wise disease progression by executing paracrine signaling that transforms the microenvironment to guide the metastatic CTCs to anchor at a conducive new organ. Random sampling of easily accessible patient blood or its serum/plasma derivatives and other bodily fluids collectively known as liquid biopsy (LB), forms an efficient alternative to tissue biopsies. In this review, we discuss in detail the divergence of early metastases as CTCs and the involvement of miRNAs as detectable blood-based diagnostic biomarkers that warrant a timely screening of cancer, serial monitoring of therapeutic response, and the dynamic molecular adaptations induced by miRNAs on CTCs in guiding primary and second-line systemic therapy.
Solitary Isolated Dural Metastasis From Lung Adenocarcinoma Mimicking Meningioma
Authors: Jun Zhang, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (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.
Abstract 075: Sociodemographic And Pregnancy Related Differences In Blood Pressure Phenotypes A Decade Following Pregnancy
Authors: Jewel Scott, Alisse Hauspurg, Matthew F Muldoon, Esa M Davis, Janet M Catov
Journal: Circulation (2022)

Introduction: Hypertensive disorders of pregnancy (HDP) such as preeclampsia are associated with a 3-fold increased risk of chronic hypertension (HTN). Office based measurements alone results in frequent HTN misclassification, prompting the need for out-of-office measurements to ensure proper classification. Hypothesis: We hypothesized that individual and neighborhood level sociodemographic factors and adverse pregnancy outcomes are different within the BP phenotypes of persistent normotension, and sustained, white-coat, masked, and isolated diastolic HTN. Methods: Data were from 401 women who gave birth between 2008 - 2009 and participated in a research study 8-10 years following pregnancy. We determined BP phenotypes by comparing the mean office BP (3 measures) and home BP (13 measures) assessed following research protocols. HTN was defined as BP ≥130/80. Sociodemographic characteristics were age, race, education, adiposity, and perceived stress. Neighborhood characteristics were from the CDC Social Vulnerability Index (i.e., socioeconomic status, household composition, minority status, housing type) measured at the census tract level, with higher values representing greater vulnerability. Chi-square determined differences in BP phenotypes for categorical data, and ANOVA for continuous data, both with Tukey correction. Results: Participants had a mean age of 37.6 (5.9), 15.1 (2.6) years of education, 34.7% (n=155) were Black and 22.8% (n=102) had a history of HDP. BMI and central adiposity were higher in all BP phenotypes compared to the normotensive group. Women with sustained HTN ( 6.2%, n=25) and isolated diastolic HTN (18.2%, n=73,) were more likely to be Black and have a history of HDP. However, only women with isolated diastolic HTN were more likely to have less education and higher stress scores. Compared to the normotensive women, those with masked HTN (n=25, 6.2%) tended to have a history of HDP. The BP phenotype groups did not differ by neighborhood level factors, although there was a trend toward lower neighborhood socioeconomic status among the isolated diastolic and masked HTN groups (p&lt; .10). Conclusion: Isolated diastolic HTN was the most common adverse BP phenotype in this sample of young women, and was more common among Black women and those with a history of HDP. Isolated diastolic HTN may be more prevalent than generally recognized in clinical practice. Research is needed to determine the long-term implications of this phenotype, especially among women with a history of HDP. BP phenotypes differed on individual characteristics and neighborhood socioeconomic status, however, neighborhood characteristics such as violence, air quality, and cohesiveness should be considered in future research. This research was supported by T32HL007560 (PIs: Thurston &amp; Gianaros, Trainee: Scott) and AHA award 16SFRN28930000 (PI: Catov).
Abstract P004: Modified Step-in-Place Test Measures Exercise Capacity And Tolerance Of Elderly Women
Authors: Vagner Raso, Victor Keihan Rodrigues Matsudo
Journal: Circulation (2022)

Purpose: This study analyzed fatigue, heart rate, maximum oxygen consumption, rate of perceived exertion, and steps at 30-second (s) intervals during a modified step-in-place test in elderly women. Methods: This was a cross-sectional analysis of 272 physically active, community-dwelling women aged 49 to 85 years. Individuals were instructed to perform as many steps in place as possible for two minutes with a knee elevation height (KH) at the midway point between the patella and iliac crest. Absolute (ABSsteps) and relative (RELsteps) steps, age-predicted maximum heart rate (pMHR), fatigue index, heart rate (HR), rate of perceived exertion (RPE), and estimated maximum oxygen consumption (VO 2 max) were evaluated at every 30-second interval. Results: ABSsteps (p&lt;0.0001), HR (p&lt;0.0001), pMHR (p&lt;0.0001), and RPE (p&lt;0.001) increased progressively over time, while RELsteps tended to be steady, except at 30s compared to 60 and 120s (p&lt;0.0001). The percentage of the pMHR was 78 ± 11 at 60s and 85 ± 12 at 120s. The percentage of the VO 2 max reached at 60s was 76 ± 4 and at 90s was 110 ± 4. The RPE at 120s was 15 ± 2. Almost two out of every three individuals achieved at least one of the criteria (pMHR &gt; 85%, or RPE &gt; 17, or both) to reach maximal effort (N=201, 63%). Approximately seven out of every ten individuals experienced fatigue (N=174, 65%). About half of the fatigued individuals had a decrease in performance that exceeded 15% (N=77, 44%). Conclusion: Our study allows us to conclude that individuals experience a progressive physiological demand with a near-maximal effort during the modified step-in-place test. This procedure provides objective endpoints for exercise capacity and tolerance which can be used for various purposes, including drug development.
Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants
Authors: Marta Gigli, Davide Stolfo, Sharon L. Graw, Marco Merlo, Caterina Gregorio, Suet Nee Chen, Matteo Dal Ferro, Alessia PaldinoMD, Giulia De Angelis, Francesca Brun, Jean Jirikowic, Ernesto E. Salcedo, Sylvia Turja, Diane Fatkin, Renee Johnson, J. Peter van Tintelen, Anneline S.J.M. Te Riele, Arthur A.M. Wilde, Neal K. Lakdawala, Kermshlise Picard, Daniela Miani, Daniele Muser, Giovanni Maria Severini, Hugh Calkins, Cynthia A. James, Brittney Murray, Crystal Tichnell, Victoria N. Parikh, Euan A. Ashley, Chloe Reuter, Jiangping Song, Daniel P. Judge, William J. McKenna, Matthew R.G. Taylor, Gianfranco Sinagra, Luisa Mestroni
Journal: Circulation (2021)

Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers.FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP-related arrhythmogenic cardiomyopathies were used for prognostic comparison.Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area - right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD.Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.