tbuckley/cabot-search huggingface dataset:
Generation of mice carrying floxed VEGFR-1 and VEGFR-2 alleles to study the effects of postnatal gene ablation on angiogenesis and hematopoiesis
Authors: Megan E. Baldwin, Xiao Huan Liang, Anja Ruchatz, Johanna Busch, Zhenyu Gu, Meron Roose-Girma, Christine Olsson, Sharon Erickson, Napoleone Ferrara, Hans-Peter Gerber
Journal: Cancer Research (2004)

2582  Vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, also known as fms-like tyrosine kinase (Flt-1) and fetal liver kinase 1 (Flk-1)/kinase insert domain receptor (KDR) respectively, are receptor tyrosine kinases that bind with high affinities to members of the VEGF family. Although both receptors bind the original member of the family, VEGF-A, they display distinct binding specificities for other VEGFs, as VEGFR-1 also binds placenta growth factor (PlGF) and VEGF-B, whereas VEGFR-2 binds VEGF-C and VEGF-D in addition to VEGF. VEGFR-1 and VEGFR-2 are predominantly expressed on vascular endothelium, but their expression has also been demonstrated on other cell types, most notably cells of the hematopoietic lineages. Targeted disruption of VEGFR-1 and VEGFR-2 expression in mice demonstrates the critical role of these receptors in vascular development. Homozygous null VEGFR-1 mice die at midgestation due to defects in hemangioblast differentiation and consequently impaired vascular formation. VEGFR-2 knockout mice fail to develop significant numbers of hematopoietic precursors and angioblasts and die at E8.5. Although the generation of such conventional knockouts has been critical for our understanding of the role of these receptors during early embryonic development, their early embryonic lethality precludes the study of the role of VEGFR-1 and VEGFR-2 during later stages of embryogenesis, in adult tissues, and during pathological situations. In addition, more recent studies focusing on the role of these receptors in hematopoiesis and endothelial cell progenitor (EPC) recruitment suggest that these receptors have important functions in addition to their role in classical vascular development. The capacity to generate tissue- or time-specific deletions of VEGFR-1 and/or VEGFR-2 would also greatly benefit these relatively new areas of research. To this end, we have generated two lines of mice, denoted VEGFR-1-LOX and VEGFR-2-LOX, in which the first coding exon and a region of the promotor of each gene is flanked by LoxP sites. To generate conditional knockouts of either receptor, mice are bred to strains that express Cre-recombinase driven by inducible (MX1-CRE) or cell-specific promoters (Tie2-CRE), resulting in excision of the DNA sequence intervening the LoxP sites and resulting in a null VEGFR-1 or VEGFR-2 allele at sites of Cre-recombinase expression. VEGFR-1-LOX and VEGFR-2-LOX mice are important tools for in vivo studies that will aid our understanding of the role of these receptors in various physiological processes.
93MO Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)
Authors: Y-S. Lu, N.S. El Saghir, S.A. Hurvitz, D. Tripathy, F. Cardoso, M.A. Colleoni, S. Campos-Gomez, F.A. Franke, R. Oregan, C. Wang, Y. Wang, J.P. Zarate, A. Chakravartty, S-A. Im
Journal: Annals of Oncology (2021)
비대상성 간경변증 환자에서 라미부딘 장기투여의 효능과 안전성에 관한 연구
Authors: 박태욱, 박영민, Si Hyun Bae, Jang Jeong Won, 남순우, Jong Young Choi, Seung-Kew Yoon, Se Hyun Cho, 양진모, 한남익, 안병민, 이창돈, 박두호, 이영석
Journal: Clinical and Molecular Hepatology (2002)

목적: 본 연구는 비대상성 간경변증 환자에서 라미부딘의 효과를 알아보고자 전향적 연구를 시행하였다. 대상과 방법: 임상적 기준에 따라 B형 간염바이러스에 의한 비대상성 간경변증으로 진단된 환자중 라미부딘을 하루 75-150 mg 씩 12개월 이상 치료한 21 명을 치료군 (남자 14명, 여자 7명 평균연령 50세, 범위 34-73세, Child-Pugh; B 등급 17명, C 등급 4명)으로 하였고, 보존적인 치료만으로 추적 검사한 20명을 대조군 (남자 17명, 여자 3명 평균연령 50세, 범위 39-61세, Child-Pugh; B 등급 15명, C 등급 5명)으로 정하고 전향적 연구를 시행하였다. 치료 전후로 HBV DNA 정량, HbeAg 정량, 혈액학적/생화학적 간기능 검사, Child-Pugh 점수 등의 소견을 비교 분석하였다. 치료 반응의 기준은 HBV DNA 와 HbeAg 음전화, ALT치 정상화 여부에 따라 반응군, Breakthrough군, 무반응군으로 정하였고, 임상적 호전의 정의는 Child-Pugh 점수가 2점 이상 감소한 경우로 하였다. 결과: 평균 관찰기간은 17개우러 (범위 12개월-26개월)이었다. 라미부딘 치료에 대한 반응군은 62% (13/21), Breakthrough군은 33% (7/21) 이고, 무반응군은 5% (1/21) 였다. 평균 Child-Pugh 점수는 치료전 8.6점에서 관찰 종료시점에 6.0점으로 호전되었지만, 대조군에서는 8.7점으로 10점으로 악화되었다. Child-Pugh 점수가 2점 이상 호전된 경우도 치료군에서 71% (15/21)였지만 대조군에서 5% (1/20)였다. HbeAg의 음전율은 치료군에서 31%(5/16) 였으나, 대조군에서는 음전화예는 없었다. 치료 후 Child-Pugh 등급 A 14명, B 6명 그리고 C가 1명이었지만, 대조군에서는 등급 B환자 15명 중 1명만이 등급 A로 호전되고 8명의 환자가 등급 C로 악화되었고, 등급 C 환자에서 임상적으로 호전된 경우는 없었다. 치료군에서 혈청 알부민, 프로트롬빈 시간, AFP 수치와 Child-Pugh 점수의 호전은 통계적으로 유의하였다 (p<0.05). 결론: 비대상성 간경변증 환자에서 라미부딘의 치료효과는 매우 고무적이며, 특히 일부 Breakthrough군이나 무반응군에서도 간기능 호전 소견을 관찰할 수 있어 향후 이에 대한 대규모 연구가 이루어져야 할 것으로 생각된다.
Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from the China pUlmonary thromboembolism REgistry Study (CURES)
Authors: Zhenguo Zhai, Dingyi Wang, Jieping Lei, Yuanhua Yang, Xiaomao Xu, Yingqun Ji, Qun Yi, Hong Chen, Xiaoyun Hu, Zhihong Liu, Yimin Mao, Jie Zhang, Juhong Shi, Zhu Zhang, Sinan Wu, Qian Gao, Xincao Tao, Wanmu Xie, Jun Wan, Yunxia Zhang, Shuai Zhang, Kaiyuan Zhen, Zhonghe Zhang, Baomin Fang, Chen Wang
Journal: European Respiratory Journal (2021)

Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies are not clear in Asian countries. We retrospectively analysed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicentre registry in China (CURES). Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analysed. Risk stratification was retrospectively classified by haemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines. Among 7438 patients, the proportions with high (haemodynamic instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. Computed tomographic pulmonary angiography was the most widely used diagnostic approach (87.6%) and anticoagulation was the most frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted p for trend =0.0003), with a concomitant reduction in the use of initial systemic thrombolysis (from 14.8% to 5.0%, p for trend &lt;0.0001). The common predictors for all-cause mortality shared by haemodynamically stable and unstable patients were co-existing cancer, older age and impaired renal function. The considerable reduction of mortality over the years was accompanied by changes in initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.
8P Mutational analysis of circulating tumour DNA (ctDNA) in patients with ER+/HER2- advanced breast cancer (ABC) receiving palbociclib (P): Results from the TREnd trial
Authors: L. Malorni, D. Romagnoli, M. Benelli, F. Galardi, C. Biagioni, G. Curigliano, A.M. Minisini, E. Moretti, E. Risi, F. De Luca, A. McCartney, A. Di Leo, L. Biganzoli, I. Migliaccio
Journal: Annals of Oncology (2021)
Furin-instructed aggregated gold nanoparticles for re-educating tumor associated macrophages and overcoming breast cancer chemoresistance
Authors: Rou Xie, Shaobo Ruan, Jiaqi Liu, Lin Qin, Chuanyao Yang, Fan Tong, Ting Lei, Maxim Shevtsov, Huile Gao, Yi Qin
Journal: Biomaterials (2021)
Matt Morgan: Covid helped me travel, with colleagues as guides
Authors: Matt Morgan
Journal: BMJ (2021)

As well as killing more than three million people worldwide, covid-19 has killed travel. Over the past year my diary has been filled with blank spaces where it used to show weekends away and long haul flights. Yet, in many ways, I have never travelled so much. I didn’t need my passport for any of these trips: they all took place in my own hospital.

As a new consultant five years ago, the first thing I did was take a mystery tour of my own hospital. I pressed the top button in the lift, going to the seventh floor, before …
Abstract 14820: Hypertensive Patients’ Perceptions of the Food Environment
Authors: Anika L Hines, Rebecca Brody, Zehui Zhou, Sarach V Collins, Chiazam Omenyi, Edgar R Miller, Lisa A Cooper, Deidra Crews
Journal: Circulation (2020)

Introduction: Poor food environment and disproportionate food insecurity among African Americans represent determinants of chronic disease disparities by race/ethnicity. The presence of a supermarket could lead to a 32 percent increase in fruit and vegetable consumption among AAs, yet a complex set of barriers may make it difficult to participate in healthy nutrition. We examined the food environment in Baltimore, MD, through the perspectives of African Americans with hypertension. Methods: Photovoice is a community-based participatory research tool that uses photography to engage participants in reflection and dialogue regarding their community's strengths, needs, and capacity for social change. We recruited 24 residents of Baltimore who met initial demographic—age (21 years or older), race (African American), and clinical criteria (hypertension) for the Five Plus Nuts and Beans for Kidneys study—a randomized control trial of a dietary intervention, but were ultimately found ineligible. After photography training, participants responded to “Photograph everything related to food in your neighborhood” and discussed their images over 4 sessions. Audiotaped conversations were analyzed for common themes. Results: Through this formative, community-engaged process, residents deemed the food environment reflective of the race of the neighborhood’s occupants with low-income Blacks consistently situated at the disadvantaged end. Participants expressed the lack of access to food—a resource that they deemed should be accessible to all—as a catalyst of crime, a point of racial injustice, and a stumbling block in improving their health. Residents identified both individual- and system-level barriers and facilitators to eating healthy foods. Conclusions: Engaging community voices and taking stock of the nuances of the food environment, including its construction and subsequent impact on residents’ outcomes, may inform clinical practice and health policy. Photos will be exhibited and used during a moderated conversation on the food environment among multiple stakeholders in Baltimore, including viable solutions to the “food desert” conditions and opportunities to address racial disparities in chronic disease.
Abstract 16004: Clinical and Hemodynamic Correlates of Exaggerated Metabolic Cost of Exercise Initiation
Authors: Mark W Schoenike, Ravi V Shah, Miguel Á Armengol de la Hoz, Thomas F Cunningham, Jasmine B Blodgett, Melissa Tanguay, John A Sbarbaro, Jennifer N Rouvina, Alyssa Kowal, Nicholas Houstis, Matthew G Nayor, Aaron L Baggish, Jennifer E Ho, Corey Hardin, Rajeev Malhotra, Gregory Lewis
Journal: Circulation (2020)

Introduction: Exercise intolerance is common in cardiovascular disease and is a cardinal manifestation of heart failure with preserved ejection fraction (HFpEF). Decreased exercise capacity is often attributed to cardiac limitations, though HFpEF is increasingly recognized to be both a metabolic and a cardiovascular disorder. Hypothesis: Patients with HFpEF will have exaggerated metabolic cost of exercise initiation with associated high expenditure of hemodynamic reserve capacity. Methods: We quantified the workload-equivalent cost of initiating exercise using cardiopulmonary exercise testing in patients with HFpEF (N=184, age 62±13, 47% women, peak VO2 13.8±3.3 ml/kg/min). Individualized VO2-work rate relationships during loaded exercise were used to derive the work-equivalents required to move extremities with zero external resistance (0 watts)—termed “internal work” (IW). Standard linear regression techniques were used for comparisons. Results: In individuals with HFpEF, the internal work (42±28 W) was often a large portion of the total workload achieved. BMI accounted for the greatest variance in IW (23%), suggesting a metabolic basis for IW. Resting measures of myocardial function and biventricular filling pressures did not measurably contribute to explanatory variance in IW, suggesting a non-cardiac origin. Individuals with HFpEF in the fourth quartile of IW (76±28W) had a dramatic hemodynamic response to exercise in pulmonary capillary wedge and mean pulmonary arterial pressures. Changes in hemodynamic measurements were more modest between quartiles of IW in the submaximal ramp period following unloaded exercise. Conclusions: Internal work is a new measure that captures the metabolic cost of initiating movement. Internal work is associated with limitations in achievable external workload as well as steep early increases in cardiac filling pressures in HFpEF. Further investigation into the pathophysiology of elevated IW is needed.
慢性代謝性アシドーシスによる2種類のアルギニンバソプレシン(AVP)受容体の遺伝子調節
Authors: Nakamura Y, Nonoguchi H, Imanishi K, Inoue T, Arima S, Nakayama M, Tomita K
Journal: Journal of the American Society of Nephrology (1995)
Pathophysiology and Therapeutic Approaches to Cardiac Amyloidosis
Authors: Jan M. Griffin, Hannah Rosenblum, Mathew S. Maurer
Journal: Circulation Research (2021)

Often considered a rare disease, cardiac amyloidosis is increasingly recognized by practicing clinicians. The increased rate of diagnosis is in part due the aging of the population and increasing incidence and prevalence of cardiac amyloidosis with advancing age, as well as the advent of noninvasive methods using nuclear scintigraphy to diagnose transthyretin cardiac amyloidosis due to either variant or wild type transthyretin without a biopsy. Perhaps the most important driver of the increased awareness is the elucidation of the biologic mechanisms underlying the pathogenesis of cardiac amyloidosis which have led to the development of several effective therapies with differing mechanisms of actions. In this review, the mechanisms underlying the pathogenesis of cardiac amyloidosis due to light chain (AL) or transthyretin (ATTR) amyloidosis are delineated as well as the rapidly evolving therapeutic landscape that has emerged from a better pathophysiologic understanding of disease development.
Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression
Authors: Josefien J. F. Breedvelt, Fiona C. Warren, Zindel Segal, Willem Kuyken, Claudi L. Bockting
Journal: JAMA Psychiatry (2021)

Depression frequently recurs. To prevent relapse, antidepressant medication is often taken in the long term. Sequentially delivering a psychological intervention while undergoing tapering of antidepressant medication might be an alternative to long-term antidepressant use. However, evidence is lacking on which patients may benefit from tapering antidepressant medication while receiving a psychological intervention and which should continue the antidepressant therapy. A meta-analysis of individual patient data with more power and precision than individual randomized clinical trials or a standard meta-analysis is warranted.To compare the associations between use of a psychological intervention during and/or after antidepressant tapering vs antidepressant use alone on the risk of relapse of depression and estimate associations of individual clinical factors with relapse.PubMed, the Cochrane Library, Embase, and PsycInfo were last searched on January 23, 2021. Requests for individual participant data from included randomized clinical trials (RCTs) were sent.Randomized clinical trials that compared use of a psychological intervention while tapering antidepressant medication with antidepressant monotherapy were included. Patients had to be in full or partial remission from depression. Two independent assessors conducted screening and study selection.Of 15 792 screened studies, 236 full-text articles were retrieved, and 4 RCTs that provided individual participant data were included.Time to relapse and relapse status over 15 months measured via a blinded assessor using a diagnostic clinical interview.Individual data from 714 participants (mean [SD] age, 49.2 [11.5] years; 522 [73.1%] female) from 4 RCTs that compared preventive cognitive therapy or mindfulness-based cognitive therapy during and/or after antidepressant tapering vs antidepressant monotherapy were available. Two-stage random-effects meta-analysis found no significant difference in time to depressive relapse between use of a psychological intervention during tapering of antidepressant medication vs antidepressant therapy alone (hazard ratio [HR], 0.86; 95% CI, 0.60-1.23). Younger age at onset (HR, 0.98; 95% CI, 0.97-0.99), shorter duration of remission (HR, 0.99; 95% CI, 0.98-1.00), and higher levels of residual depressive symptoms at baseline (HR, 1.07; 95% CI, 1.04-1.10) were associated with a higher overall risk of relapse. None of the included moderators were associated with risk of relapse.The findings of this individual participant data meta-analysis suggest that regardless of the clinical factors included in these studies, the sequential delivery of a psychological intervention during and/or after tapering may be an effective relapse prevention strategy instead of long-term use of antidepressants. These results could be used to inform shared decision-making in clinical practice.
Abstract 16121: Wellness in Pediatric Cardiac Intensivists - How are We Doing?
Authors: David K Werho, leslie rhodes, Robin Horak, Bradley S Marino, David S Cooper, Antonio G Cabrera, John M Costello, Shasha Bai, Yubo Tan, Sarah Tabbutt, Catherine D Krawczeski
Journal: Circulation (2020)

Introduction: Poor physician wellness is associated with detrimental effects on patient outcomes. There are no data on physician wellness in pediatric cardiac critical care. We aimed to define the prevalence of and risk factors for impaired wellness using a targeted survey of the North American pediatric cardiac critical care workforce. Methods: We developed a survey to examine physician wellness and potential risk factors, incorporating the Expanded Physician Well Being Index. Unit directors at 120 congenital heart surgery centers were contacted to provide faculty emails. The survey was distributed to each faculty with targeted reminders from June - September 2019. Univariate and multivariable logistic regression analyses were performed comparing the at-risk respondents to those not at risk for poor wellness. Results: Of the 477 faculty, 294 completed the survey (62%). Faculty reported working a median of 83 hours on service weeks and 50 hours on non-service weeks. Based on Well-Being scores, 34% were in the “at risk” category; 56% reported feeling burned out in the past month and 46% reported feeling overwhelmed. However, 96% felt their work was meaningful. Faculty reported a high incidence of developing unhealthy habits including poor nutrition (50%), infrequent exercise (56%), and lack of self-care (46%). Factors associated with well-being risk are shown in Table 1. Poor interpersonal experiences, higher work hours, and being primarily trained in critical care with an additional cardiac year were associated with risk of poor wellness. Working &gt;100 hours per service week had a significant increase in risk (odds ratio 2.3, 95% confidence interval 1.31-4.40). Availability of wellness services was associated with reduced risk. Conclusion: Burnout and risk of poor wellness are common in pediatric cardiac critical care faculty. Modifiable factors, including wellness service availability and reduced hours of clinical service may improve wellness in the workforce.
Pretreatment Risk Stratification for Endoscopic Kidney-sparing Surgery in Upper Tract Urothelial Carcinoma: An International Collaborative Study
Authors: Beat Foerster, Mohammad Abufaraj, Surena F. Matin, Mounsif Azizi, Mohit Gupta, Wei-Ming Li, Thomas Seisen, Timothy Clinton, Evanguelos Xylinas, M. Carmen Mir, Donald Schweitzer, Andrea Mari, Shoji Kimura, Marco Bandini, Romain Mathieu, Ja H. Ku, Gautier Marcq, Georgi Guruli, Markus Grabbert, Anna K. Czech, Tim Muilwijk, Armin Pycha, David D’Andrea, Firas G. Petros, Philippe E. Spiess, Trinity Bivalacqua, Wen-Jeng Wu, Morgan Rouprêt, Laura-Maria Krabbe, Kees Hendricksen, Shin Egawa, Alberto Briganti, Marco Moschini, Vivien Graffeille, Wassim Kassouf, Riccardo Autorino, Axel Heidenreich, Piotr Chlosta, Steven Joniau, Francesco Soria, Phillip M. Pierorazio, Shahrokh F. Shariat
Journal: European Urology (2021)

Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC).To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models.This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017.We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models.Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p < 0.001), biopsy cT1+ staging (OR 3.23, 95% CI 1.93-5.41, p < 0.001), preoperative hydronephrosis (OR 1.37 95% CI 1.04-1.80, p = 0.024), tumor size (OR 1.09, 95% CI 1.01-1.17, p = 0.029), invasion on imaging (OR 5.10, 95% CI 3.32-7.81, p < 0.001), and sessile architecture (OR 2.31, 95% CI 1.58-3.36, p < 0.001) were significantly associated with ≥pT2/pN+ disease. Compared with the existing models, our model had the highest performance accuracy (75% vs 66-71%) and an additional clinical net reduction (four per 100 patients).Our proposed risk-stratification model predicts the risk of harboring ≥pT2/N+ UTUC with reliable accuracy and a clinical net benefit outperforming the current risk-stratification models.We developed a risk stratification model to better identify patients for endoscopic kidney-sparing surgery in upper tract urothelial carcinoma.
Covid-19: Government must invest in primary care to aid pandemic recovery, say leaders
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Primary care is under "immense pressure" and needs investment, clear national priorities, and new mechanisms to measure workload in order to restore services and support staff in the aftermath of the covid-19 pandemic, leaders have said.In a paper 1 published on 10 May, the NHS Confederation highlighted the increasing and unsustainable workload facing primary care services as they provide routine care while also seeing patients with long covid, those with multiple comorbidities and long term conditions, people waiting for elective care, and the growing number requiring mental health support. 2