tbuckley/cabot-search huggingface dataset:
Abstract 11432: The Impact of Regional Adipose Tissue Deposition on Physical Activity in Heart Failure with Preserved Ejection Fraction
Authors: Katlyn Koepp, Zachary S Quicksall, Yogesh Reddy, Masaru Obokata, Hidemi Sorimachi, Frederik Verbrugge, Alexander C Egbe, Eric Bruhn, Rickey Carter, Barry A Borlaug, Thomas P Olson
Journal: Circulation (2021)

Introduction: Obesity is common in heart failure with preserved ejection fraction (HFpEF) and is directly linked with lower levels of physical activity (PA). Visceral adiposity (VAT) is more common in HFpEF than controls and may play a role in its pathogenesis, characterized by impaired exercise capacity (peak VO 2 ). The direct relationship between VAT and PA in HFpEF is unknown. Hypothesis: Compared to controls, HFpEF patients will have excess regional adiposity (VAT, subcutaneous (SAT), and intramuscular (IMAT)), and these fat depots will be associated with lower levels of chronic physical activity. Methods: HFpEF patients (n=51; age 70±9) and non-HFpEF controls (n=49; age 65±5) prospectively underwent body composition measurement by dual-energy x-ray absorptiometry and magnetic resonance imaging. Peak VO 2 was measured by standard cardiopulmonary exercise testing. PA was monitored continuously via accelerometry over two weeks. Data were binned in arbitrary accelerometry units, averaged and stored in 30-second epochs (counts per epoch, CPE). Models were adjusted for age, sex, and ideal body weight. Results: HFpEF were less active overall (3.15±0.80 vs 3.59±0.73 CPE), had less moderate intensity PA (10.13±0.04 vs 10.15±0.03 CPE), and less morning (3.83±1.15 vs 4.24±1.09 CPE) and afternoon (3.84± 1.20 vs 4.53± 0.97 CPE) (p&lt;0.05 for all) PA. Patients with HFpEF spent a greater proportion of time sedentary (0.71±0.08 vs 0.67±0.08 CPE) and less time in moderate (0.04±0.03 vs 0.06±0.03 CPE) and vigorous (0.02±0.01 vs 0.03±0.03 CPE) PA (p&lt;0.01 for all). Chronic PA was significantly associated with regional fat depots (VAT β= -0.003, 95% CI: -0.004-0.001; SAT β= -0.003, 95%CI: -0.004-0.001; IMAT β=-0.02, 95% CI: -0.04—0.01) as a combined cohort (p&lt;0.01 for all). Muscle quality (β=0.28, 95%CI: 0.15-0.40), peak VO 2 (β=0.08, 95% CI: 0.03-0.13), and peak watts (β=0.01, 95% CI: -0.004-0.02) were associated with PA in HFpEF only (p≤0.01 for all). Conclusions: The amount and pattern of PA differs between HFpEF and controls, as do relationships between regional fat depots and PA, and the relationship of PA and peak VO 2 . Further investigation is needed to better understand the temporality and mechanisms related to the pathophysiology and severity of HFpEF.
Abstract 11585: Determination of Aortic and Mitral Valve Opening and Closing Times Using Only LV Pressure Data
Authors: M. Rifqi Aufan, Neal J Miller, Zachary T Jost, Oleg F Sharifov, Himanshu Gupta, Thomas S Denney, Steven G Lloyd
Journal: Circulation (2021)

Background: Identification of aortic and mitral valve opening and closure timing is crucial for assessment of left ventricle (LV) function, e.g. pressure-volume loops. This is particularly problematic when simultaneous imaging (e.g. echocardiography) is not available. We hypothesize that LV pressure and its time derivatives can detect valve opening and closure times. Our aim was to determine the aortic and mitral valve opening and closures using properties of the LV pressure waveform. Methods: For this pilot study, in 3 human participants in sinus rhythm, LV pressures were recorded with a high-fidelity catheter. Echocardiographic 2D-guided M-mode images were obtained across the aortic and mitral valves in the parasternal long axis view. The timing of aortic and mitral valve events was linked to the ECG tracing, using the peak of the ECG R wave as the reference point. For each participant, two consecutive heartbeats were selected and the first (dP/dt), second (d 2 P/dt 2 ), and third derivatives (d 3 P/dt 3 ) of LV pressure calculated. Local maxima and minima from these were compared with the valve timing from M-mode. Results: The maximum of dP/dt at the beginning of the systolic phase occurred consistently with the opening of the aortic valve. Local minimum and maximum d 2 P/dt 2 occurred at the closure of the aortic valve and pre-atrial contraction timing, respectively. The early diastolic minimum of d 3 P/dt 3 and early systolic maximum of d 3 P/dt 3 coincided with M-mode mitral valve opening and closure timing, respectively. There was a strong correlation between the valve events timing that was measured using these two methods (R 2 =0.98, p&lt;0.001). Conclusion: Aortic and mitral valve timing defined using LV pressure waveform agrees with valve opening/closure timing determined using echo M-mode as the gold standard. Determination of these valve timings is helpful for advanced analysis of LV mechanics when simultaneous echocardiography is not available.
Abstract 14060: Gender Difference in Atherosclerotic Plaque Characteristics and Vascular Morphology Features by Coronary CTA in Coronary Artery Disease With and Without Ischemia (CREDENCE Substudy)
Authors: Suraj Dahal, Rebecca A Jonas, Tami Crabtree, Ahmed M Shafter, Suvasini Lakshmanan, Venkat Manubolu, Robert S Jennings, Andrew Choi, James K Min, James P Earls, Matthew Budoff
Journal: Circulation (2021)

Introduction: It is unknown whether gender differences exist in the atherosclerotic plaque characteristics (APCs) and vessel morphology of patients with and without ischemia. Hypothesis: There are no gender differences in the APCs or vessel morphology of patients with and without ischemia. Methods: The 303 patients in the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) trial were enrolled following referral for non-emergent invasive coronary angiography with 3-vessel FFR and subsequently underwent CCTA per study protocol. Ischemic vessels were defined by FFR &lt; 0.8 or vessel diameter stenosis &gt; 90% on invasive investigation. A blinded quantitative analysis using artificial intelligence software was used to quantify APCs visualized on CCTA throughout the coronary tree (Cleerly Labs, Cleerly Inc., New York). APCs and vessel morphology data were stratified by gender for further analysis. Results: Among the 303 patients in the study cohort, 162 (53.4%) patients (22.8% females) had ischemic vessels and 141 (46.6%) patients (36.2% females) had non-ischemic vessels. While men were more likely to use tobacco ( p &lt;0.0001), there were no other gender differences in the age or comorbidity profile of the cohort. On imaging, men had more total plaque (non-ischemic group only) ( p =0.018), low-density non-calcified plaque and non-calcified plaque (NCP) volume, as well as greater lesion length, and lumen volume than females. There were no gender differences in calcified plaque, remodeling, high risk plaques, stenosis diameter, or APCs normalized for vessel volume (PAV). Conclusion: In patients with and without ischemia, men have a higher prevalence of low-density NCP and total NCP volume, with no significant differences in remodeling or other atherosclerotic features. These composition plaque differences may be useful to determine gender-specific risks of coronary ischemia as compared to invasive FFR.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context
Authors: Marcel Morgenstern, Christian D. Peikert, Philipp Lübbert, Ida Suppanz, Cinzia Klemm, Oliver Alka, Conny Steiert, Nataliia Naumenko, Alexander Schendzielorz, Laura Melchionda, Wignand W.D. Mühlhäuser, Bettina Knapp, Jakob D. Busch, Sebastian B. Stiller, Stefan Dannenmaier, Caroline Lindau, Mariya Licheva, Christopher Eickhorst, Riccardo Galbusera, Ralf M. Zerbes, Michael T. Ryan, Claudine Kraft, Vera Kozjak-Pavlovic, Friedel Drepper, Sven Dennerlein, Silke Oeljeklaus, Nikolaus Pfanner, Nils Wiedemann, Bettina Warscheid
Journal: Cell Metabolism (2021)

Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases. Different views exist on the composition of the human mitochondrial proteome. We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). We identified interactors of translocases, respiratory chain, and ATP synthase assembly factors. The abundance of MitoCoP proteins covers six orders of magnitude and amounts to 7% of the cellular proteome with the chaperones HSP60-HSP10 being the most abundant mitochondrial proteins. MitoCoP dynamics spans three orders of magnitudes, with half-lives from hours to months, and suggests a rapid regulation of biosynthesis and assembly processes. 460 MitoCoP genes are linked to human diseases with a strong prevalence for the central nervous system and metabolism. MitoCoP will provide a high-confidence resource for placing dynamics, functions, and dysfunctions of mitochondria into the cellular context.
Impact of Natural Killer Cells Reconstitution on Outcomes after Allogenic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis
Authors: Moazzam Shahzad, Amna Y Shah, Muhammad Usman Zafar, Ezza Tariq, Anam Hamid, Ayna Serwat, Iqra Anwar, Sibgha Gull Chaudhary, Ramesh Balusu, Rajat Bansal, Nausheen Ahmed, Leyla Shune, Joseph P. McGuirk, Muhammad Umair Mushtaq
Journal: Blood (2021)
Molecular Biomarker Testing and Targeted Therapy Patterns in Patients with Acute Myelogenous Leukemia (AML) in Community Health Systems in the United States: A Real-World Data Analysis
Authors: Francesca Coutinho, Zartash Gul, Anna B. Berry, Michael A. Thompson, Christopher Allen Willner, Sowjanya Vuyyala, Haley McCracken, Katherine Geverd, Jeanna Wallenta Law, Frank M. Wolf, Thomas D. Brown, Philip Kuriakose
Journal: Blood (2021)
Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study on Patients with Acute Myeloid Leukemia
Authors: Naoko Hosono, Takahiro Yamauchi, SungGi Chi, Kentaro Fukushima, Hirohiko Shibayama, Seiichiro Katagiri, Akihiko Gotoh, Motoki Eguchi, Takanobu Morishita, Reiki Ogasawara, Takeshi Kondo, Masamitsu Yanada, Kazuhito Yamamoto, Tsutomu Kobayashi, Junya Kuroda, Kensuke Usuki, Yoshikazu Utsu, Nobuyuki Aotsuka, Makoto Yoshimitsu, Kenji Ishitsuka, Takaaki Ono, Naoto Takahashi, Satoshi Iyama, Makoto Nakamura, Yukinori Nakamura, Suguru Fukuhara, Koji Izutsu, Nobuhiko Yamauchi, Junichiro Yuda, Yosuke Minami
Journal: Blood (2021)
Molecular Evolution of Classical Hodgkin Lymphoma Revealed Though Whole Genome Sequencing of Hodgkin and Reed-Sternberg Cells
Authors: Francesco Maura, Marcin Imielinski, Jenny Z Xiang, Bhavneet Binder, Kenneth Eng, Manik Uppal, Feng He, Wei Zhang, Qi Gao, Sunita I. Park, Matthew J. Oberley, Elizabeth Ruckdeschel, Megan S. Lim, Gerald Wertheim, Matthew J. Barth, Terzah M. Horton, Bachisio Ziccheddu, Federico Abascal, Kylee H Maclachlan, Venkata D Yellapantula, Ola Landgren, Craig H. Moskowitz, Ethel Cesarman, Mikhail Roshal, Olivier Elemento, Lisa Giulino Roth
Journal: Blood (2021)
Abstract 12358: Oral Iron Supplementation is Associated With Lower Pulmonary Vascular Resistance in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
Authors: Yicheng Tang, Ashish B Patel, Haris Rahman, Sae K Jang, Adam Handen, Gavin W Hickey, Neil Kelly, Stephen Y Chan
Journal: Circulation (2021)

Introduction: Pulmonary hypertension (PH) associated with left heart disease can be stratified as isolated post-capillary (IpcPH) or combined pre and postcapillary (CpcPH) on the basis of a normal or elevated pulmonary vascular resistance (PVR). While CpcPH carries a poor prognosis, the mechanistic determinants of PVR in this population remain undefined. We hypothesize that discrepant medication usage between hemodynamic extremes of IpcPH and CpcPH may underlie this phenotypic divergence. Methods: Invasive hemodynamics were obtained at UPMC between 2008 and 2018. 4,567 patients met diagnostic criteria for Group 2 PH (mean pulmonary artery pressure [mPAP] ≥ 25mmHg, pulmonary artery wedge pressure [PAWP] &gt; 15mmHg) based on the 2013 definition. Patients were classified as having extreme IpcPH (PVR&lt;2WU, N=414) or CpcPH (PVR&gt;4WU, N=172). Patients with overlapping PH diagnoses were excluded. Preserved ejection fraction was defined as a left ventricular EF &gt;40%. Follow-up analyses were conducted on an independent set of PH-HFpEF patients with two RHCs more than 90 days apart inclusive of all PVRs (N=46). Results: Compared to IpcPH (N=127), patients with CpcPH (N=47) were prescribed anticoagulants (53.19 vs. 19.69%, p&lt;0.001) more frequently and oral iron supplements less frequently (4.26 vs. 20.47%, p=0.010). Red cell distribution width (RDW), a marker of iron deficiency, was significantly higher in CpcPH (16.57 vs. 15.24%, p=0.007). In PH-HFpEF patients with successive RHCs, change in PVR correlated positively with change in RDW (p=0.002). Compared to iron naïve patients (N=30), iron initiation (N=7) between RHCs was associated with a lower change in PVR (-1.05 vs. +0.66WU, p=0.008). Conclusions: In a PH-HFpEF cohort, iron supplementation was associated with lower PVR, suggesting that iron deficiency may contribute to vascular remodeling in PH-HFpEF.
Abstract 12770: Using the Socioecological Model to Explore Barriers to Healthcare Provision in Rural Communities in the Philippines
Authors: Lorraine S Evangelista, Elizabeth Lorenzo
Journal: Circulation (2021)

Background: Basic healthcare in the Philippines is provided via rural healthcare clinics (RHC) located in barangays and supervised by provincial health centers. These RHC are the cornerstone of the country's public health system and were designed to promote and prevent disease through basic healthcare services and education. However, RHC became nonfunctional during the COVID pandemic leaving the community without the resources necessary to address the acute problems associated with COVID and chronic conditions. Given the crucial role of RHC in disease prevention and control, identifying barriers to providing its services and programs is warranted. Aims: The purpose of this qualitative study was to explore multilevel barriers to the provision of healthcare services and education in RHC. Methods: We used a qualitative approach and the socioecological model as a framework to investigate the multilevel barriers affecting resource access at RHC. Four public health nurses and fifteen community healthcare workers (CHW) from five RHC across the country participated in individual interviews and group discussions. Traditional content analysis was used to examine the data. Results: Findings revealed barriers at the individual (insufficient motivation, incorrect beliefs), interpersonal (insufficient ability of CHW to provide services, and lack of training, unrealistic expectations, and lack of supervision and monitoring of CHW), organizational (excessive workload for CHW, lack of resources, inadequacy of evaluation and monitoring of CHW), community (lack of trust in CHW by people, lack of motivation to seek healthcare, continued belief in traditional healers), and policy (lack of financial support for RHC, lack of an organized system to meet community needs) levels. Conclusion: Examining individual, interpersonal, community, and policy level determinants that affect RHC can inform community-based health promotion interventions for the country's rural communities. Given the multidimensional barriers identified, it is recommended that a comprehensive program be developed and implemented in collaboration with licensed healthcare providers, CHW, district and regional healthcare department representatives, and healthcare policymakers.
CTNI-54. A SINGLE ARM PHASE II STUDY OF THE DUAL MTORC1/MTORC2 INHIBITOR VISTUSERTIB PROVIDED FOR SPORADIC PATIENTS WITH GRADE II-III MENINGIOMAS THAT RECUR OR PROGRESS AFTER SURGERY AND RADIATION
Authors: Scott Plotkin, Priya Kumthekar, Patrick Wen, Fred Barker, Roberta Beauchamp, Elizabeth Gerstner, Alona Muzikansky, Miriam Smith, Anat Stemmer-Rachamimov, Justin Jordan, Vijaya Ramesh
Journal: Neuro-Oncology (2021)

Abstract Grade II/III meningiomas have increased rates of recurrence with no approved medical therapies. The historical progression-free survival at 6 months (PFS-6) is 25% with rates &amp;gt;35% declared of interest for drug development. NF2 gene inactivation occurs in about half of meningiomas. Based on our studies showing mTORC1 and mTORC2/SGK1 pathway activation in NF2-deficient meningiomas and the paradoxical activation of the mTORC2/AKT pathway, we hypothesized that mTORC1/mTORC2 inhibitors would be active in meningiomas. We studied the effect of vistusertib in patients with progressive/recurrent grade II/III meningiomas (NCT03071874). Vistusertib was administered orally at 125mg twice daily on two consecutive days each week. MRIs were obtained every 56 days. Tumor size was defined as the largest cross-sectional area. Progression was defined as ≥ 25% increase in the sum of products of all measurable lesions over smallest sum observed. The primary endpoint was PFS-6. Secondary endpoints included toxicity, radiographic response, and correlative studies including immunohistochemistry for mTORC1/2 pathway activation and genetic biomarkers. Twenty-eight patients (13 female, median age 58 years, median KPS 80%) were enrolled. Median tumor size was 4.4cm; 71% were grade II and 50% harbored pathogenic NF2 variants. Four patients discontinued treatment voluntarily and 1 each withdrew for intercurrent illness and non-compliance. PFS-6 is 47% (CI, 26%-65%) and OS-12 is 72% (95%CI, 48%-86%). PFS but not OS was shorter for patients with grade 3 meningiomas; there was no difference in PFS/OS between genetic groups. Adverse events at least possibly related to vistusertib with frequency &amp;gt;10% include nausea, fatigue, hypophosphatemia, diarrhea, anorexia, dry mouth, hypertriglyceridemia, hypertension, vomiting, increased ALT, constipation, and weight loss. Vistusertib treatment was associated with a PFS-6 rate exceeding the target of 35% for recurrent high-grade meningioma. Adverse events were tolerable in this patient population. These data support the continued development of mTORC1/2 inhibitors in this setting.
Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA
Authors: Thierry Facon, Gordon Cook, Saad Z. Usmani, Cyrille Hulin, Shaji Kumar, Torben Plesner, Cyrille Touzeau, Nizar J. Bahlis, Supratik Basu, Hareth Nahi, Hartmut Goldschmidt, Hang Quach, Mohamad Mohty, Christopher P. Venner, Katja Weisel, Noopur Raje, Benjamin Hebraud, Karim Belhadj-Merzoug, Lotfi Benboubker, Olivier Decaux, Salomon Manier, Denis Caillot, Jon Ukropec, Huiling Pei, Rian Van Rampelbergh, Clarissa M. Uhlar, Rachel Kobos, Sonja Zweegman
Journal: Leukemia (2022)

Abstract In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P &lt; 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10 –5 ) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.
Patients concerns inventory (PCI) versus standard treatment pathway in the management of patients with head and neck cancer: a qualitative informed economic evaluation
Authors: Victory ‘Segun Ezeofor, Llinos Haf Spencer, Simon N Rogers, Anastasios Kanatas, Derek Lowe, Cherith J Semple, Jeffrey R Hanna, Seow Tien Yeo, Rhiannon Tudor Edwards
Journal: The Lancet (2021)
INNV-29. BILATERAL PARIETAL LYMPHOMA LESIONS RESPONDED DIFFERENTLY TO HD-MTX AND RITUXIMAB/TEMOZOLOMIDE THERAPY
Authors: Xiao-Tang Kong, Steven Du, Yoon Jae Choi, Daniela Bota
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Primary CNS lymphoma is a rare aggressive hematological malignancy. Current chemotherapy for induction phase is HD-MTX single agent or HD-MTX based combination regimen. We report a rare case whose left and right parietal lymphoma lesions in the brain responded to different induction therapy regimens during the induction phase. CASE REPORT A 43-year-old female presented with seizure and her brain MRI showed bilateral parietal brain lesions in January of 2020. Biopsy and work-up revealed primary CNS diffuse large B-cell lymphoma (DLBCL). The patient underwent HD-MTX therapy. Brain MRI showed clear progression of left parietal lymphoma but stable right parietal lymphoma after two cycles of HD-MTX at 8 g/m2. The treatment was switched to a rituximab 750 mg/m2 weekly and temozolomide 150 mg/m2 daily one-week-on and one-week-off regimen. After 8 weeks, her brain MRI showed nearly complete response of her left parietal lymphoma to rituximab/temozolomide but progression of her right parietal lymphoma. She was switched back to HD-MTX and completed total 8 cycles. Her right parietal lymphoma lesion showed complete response to HD-MTX. The patient is doing well and has been off the treatment over the past 10 months and is waiting for consolidation therapy with autologous stem cell transplantation that has been postponed due to the COVID pandemic. DISCUSSION Our case highlights the very rare heterogenous feature of primary CNS lymphoma responding to different treatment regimen. Biopsy of bilateral heterogeneous lesions may be indicated to compare the different molecular features of the lymphoma to find underlying mechanism if they respond to treatment differently. Specific treatment regimen should be selected based on the responsiveness of CNS lymphoma lesions or combination therapy is selected to cover the heterogeneous susceptibility to chemotherapy regimens.
Oriented nanofibrous P(MMD-co-LA)/Deferoxamine nerve scaffold facilitates peripheral nerve regeneration by regulating macrophage phenotype and revascularization
Authors: Xianzhen Dong, Ping Wu, Lesan Yan, Kun Liu, Wenying Wei, Qiang Cheng, Xinyue Liang, Yun Chen, Honglian Dai
Journal: Biomaterials (2021)