tbuckley/cabot-search huggingface dataset:
Abstract P267: Paradoxical Association Between Breastfeeding Duration and Hypertension in Later Years in Parous Korean Women: A Nationwide, Population-based Study
Authors: Hong Seok Lee, Kyong-Do Han, Yong-Moon Park
Journal: Circulation (2017)

Background: The World Health Organization (WHO) recommends exclusive breastfeeding from birth to 6 months, the introduction of nutritious complementary foods at 6 months and continued breastfeeding up to 2 years or above. A U-shaped association between duration of breastfeeding and systolic blood pressure (BP) or hypertension was reported. However, multiple studies have yielded inconsistent findings. Method: Among subjects who participated in the Korea National Health and Nutrition Examination Survey conducted in 2010-2012, a total of 5,011 parous female, aged over 19 years old were analyzed. Hypertension was defined based on JNC 8 guidelines, or a self-reported current use of antihypertensive medications. Based on the JNC 8 criteria, for patients 60 years of age or older who did not have diabetes or chronic kidney disease, a blood pressure goal of less than 150/90 mmHg was the target goal or diagnosis. The blood pressure goal of diagnosis and control is less than 140/90 mmHg for patients 18 to 59 years of age without major comorbidities, and those 60 years of age or older who had diabetes, chronic kidney disease, or both conditions. We divided the duration of breast feeding into none, less than 6 months, less than 1 year and more than 6 months, less than 2 years and more than 1 year, and more than 2 years. Results: The distribution of systolic and diastolic BP and hypertension prevalence showed U-shape pattern in non-obese women (BMI &lt; 25 kg/m 2 ). Those who breastfed less than 6 months had the lowest blood pressure (123.7±1.1 mmHg for mean systolic BP and 74.2±0.7 mmHg for mean diastolic BP; P=0.06), as well as the lowest prevalence of hypertension (14.6%; P &lt; 0.001) in non-obese women. With increasing duration of breastfeeding, no specific trend was observed in obese women. In non-obese women with BMI &lt; 25 kg/m 2 , compared to women with duration of breast feeding less than 6 months, the odds of hypertension was significantly higher in women with breast feeding more than 2 years in women with [odds ratio (OR): 1.72, 95 % confidence interval (CI): 1.10-2.70], after adjusting for age, body mass index, smoking, drinking alcohol, exercise, income, and education. However, there was no significant association between duration of breastfeeding and hypertension control. Conclusion: Our findings suggest that longer duration of breastfeeding might not protect against hypertension in later ages. Previously,breast feeding could be helpful to mother after delivery to normalize her body weight, metabolic panel derangement, however, longer duration of breast feeding especially in non-obese women would not contribute to hypertension prevention. Further prospective studies are warranted to confirm this association.
Human Cartilage Homogenates Influence the Crystallization of Monosodium Urate and Inflammatory Response to Monosodium Urate Crystals: A Potential Link Between Osteoarthritis and Gout
Authors: Ashika Chhana, Bregina Pool, Yicheng Wei, Ally Choi, Ryan Gao, Jacob Munro, Jillian Cornish, Nicola Dalbeth
Journal: Arthritis & Rheumatology (2019)

Monosodium urate (MSU) crystal deposition and gout flares frequently affect osteoarthritic joints. This study was undertaken to examine the effects of human cartilage homogenates on MSU crystallization and MSU crystal-induced inflammation.Human cartilage homogenates were prepared from macroscopically healthy and macroscopically diseased knee joint samples. Crystallization assays were used to test the effects of cartilage homogenates or individual cartilage factors on MSU crystallization. Changes in urate solubility, crystal nucleation, crystal growth, and total crystal mass were determined. THP-1 cell assays were used to assess cytokine release following culture with MSU crystals grown in the presence or absence of cartilage homogenates or individual proteins.Addition of either 5% or 10% healthy cartilage homogenate increased the total mass of MSU crystals formed and resulted in formation of shorter MSU crystals compared to controls without cartilage homogenate. MSU crystal bows were observed in both the presence and absence of cartilage homogenate; however, bows formed in the presence of cartilage homogenates were significantly shorter than bows formed in their absence. There were no effect differences between macroscopically healthy and macroscopically diseased cartilage homogenates in all assessments. Addition of either type II collagen or albumin also led to the formation of shorter MSU crystals. In THP-1 cell assays, MSU crystals grown with healthy cartilage homogenate increased the release of interleukin-8, whereas MSU crystals grown with type II collagen or albumin had no effect on inflammatory cytokine release.In the presence of elevated urate levels, human cartilage homogenates increase MSU crystal formation and promote the formation of smaller crystals, which have greater inflammatory potential. These processes may contribute to the predilection of osteoarthritic joints to develop gout.
Antisense Oligonucleotide Therapies for Neurodegenerative Diseases
Authors: C. Frank Bennett, Adrian R. Krainer, Don W. Cleveland
Journal: Annual Review of Neuroscience (2019)

Antisense oligonucleotides represent a novel therapeutic platform for the discovery of medicines that have the potential to treat most neurodegenerative diseases. Antisense drugs are currently in development for the treatment of amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease, and multiple research programs are underway for additional neurodegenerative diseases. One antisense drug, nusinersen, has been approved for the treatment of spinal muscular atrophy. Importantly, nusinersen improves disease symptoms when administered to symptomatic patients rather than just slowing the progression of the disease. In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs. Based in part on the early success of nusinersen, antisense drugs hold great promise as a therapeutic platform for the treatment of neurological diseases.
A Phase 0 Trial of Ribociclib in Recurrent Glioblastoma Patients Incorporating a Tumor Pharmacodynamic- and Pharmacokinetic-Guided Expansion Cohort
Authors: An-Chi Tien, Jing Li, Xun Bao, Alanna Derogatis, Seongho Kim, Shwetal Mehta, Nader Sanai
Journal: Clinical Cancer Research (2019)

CDK4/6-dependent cell-cycle regulation is disrupted in most glioblastomas. This study assesses the central nervous system (CNS) pharmacokinetics and tumor pharmacodynamics of ribociclib, a highly selective CDK4/6 inhibitor, in patients with recurrent glioblastoma.
Beyond JAK2 Inhibitors: A Systematic Review of Management Strategies for Myelofibrosis
Authors: Ali Younas Khan, Nimra Iftikhar, Awais Ijaz, Muhammad Junaid Tariq, Faiza Jamil, Arshia Akbar, Anum Qureshi, Jemin Aby Jose, Ahmad Kamal, Muhammad Abu Zar, Madeeha Shafqat, Insija Ilyas Selene, Shehroz Aslam, Faiz Anwer
Journal: Blood (2018)
Global Prevalence of Colorectal Neoplasia: A Systematic Review and Meta-Analysis
Authors: Martin C.S. Wong, Junjie Huang, Jason L.W. Huang, Tiffany W.Y. Pang, Peter Choi, Jingxuan Wang, Jason I. Chiang, Johnny Yu Jiang
Journal: Clinical Gastroenterology and Hepatology (2019)

Most colorectal cancers (CRC) arise from colorectal adenomas, yet there is not enough information on global prevalence to inform health care policy. We examined the prevalence of any type of adenomas, advanced adenomas (AADs), and CRC according to age, sex, ethnicity, geographic regions, and anatomic location (proximal vs distal).MEDLINE and Embase were searched from their inception through May 1, 2018, to identify population-based, observational studies that reported the prevalence of colorectal neoplasia. Studies on participants 15 years or older, with a sample size of 500 persons or more, were included. Metaprop (College Station, TX) was used to model within-study variability by binomial distribution and Freeman-Tukey Double Arcsine Transformation to stabilize the variances. The prevalence figures were presented by proportions and their 95% CIs using random-effects models.Our meta-analysis included 70 studies involving 637,414 individuals. The overall prevalence rates of adenoma (23.9%; 95% CI, 22.2%-25.8%), AAD (4.6%; 95% CI, 3.8%-5.5%), and CRC (0.4%, 95% CI, 0.3%-0.5%) were calculated. Subgroup analysis indicated that prevalence values (adenomas, AADs, and CRCs) were higher among men (29.7%, 6.5%, and 0.8%, respectively) than women (19.3%, 3.8% and 0.4%, respectively), among older adults (25.9%, 5.2%, and 0.6%, respectively) than younger adults (14.6%, 1.6%, and 0.1%, respectively), among Caucasians (23.7%, 6.6%, and 0.5%, respectively) than other ethnicities, in European countries (25.9%, 8.4%, and 0.8%, respectively) than other countries, and among patients with proximal (25.9%, 5.3%, and 0.1%, respectively) vs distal neoplasia.In a systematic review and meta-analysis, we found a high prevalence of colorectal neoplasia among some populations. This indicates a need to expand CRC screening programs for these groups. The pooled prevalence estimates can be used as quality indicators for established CRC screening programs.
Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department
Authors: Kavitha M. Chinnaiyan, Robert D. Safian, Michael L. Gallagher, Julie George, Simon R. Dixon, Abhay N. Bilolikar, Amr E. Abbas, Mazen Shoukfeh, Marc Brodsky, James Stewart, Elvis Cami, David Forst, Steven Timmis, Jason Crile, Gilbert L. Raff
Journal: JACC. Cardiovascular imaging (2019)
Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps
Authors: Yoji Takeuchi, Katsuhiro Mabe, Yuichi Shimodate, Shinji Yoshii, Shinya Yamada, Mineo Iwatate, Takuji Kawamura, Kinichi Hotta, Koji Nagaike, Nobuaki Ikezawa, Tomoaki Yamasaki, Yoriaki Komeda, Satoshi Asai, Yasuhiro Abe, Takuji Akamatsu, Yuko Sakakibara, Hisatomo Ikehara, Yuzuru Kinjo, Takashi Ohta, Yoko Kitamura, Takashi Shono, Takuya Inoue, Yoshio Ohda, Nozomu Kobayashi, Tokuma Tanuma, Ryu Sato, Taku Sakamoto, Naohiko Harada, Akiko Chino, Hideki Ishikawa, Masanori Nojima, Toshio Uraoka
Journal: Annals of Internal Medicine (2019)

Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP).To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps.Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355).30 Japanese institutions.Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp.Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy.The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP).A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group.An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously.Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP.Japanese Gastroenterological Association.
The changing face of phase I protocols: A closer look at study requirements
Authors: B. S. Craft, R. Kurzrock, R. Herbst, K. Culotta, C. Stewart, V. Dorsey, S. Lippman, D. Gingher, N. Bekele, D. Karp
Journal: Journal of Clinical Oncology (2007)

3061 Background: We have studied our recent experience in the MDACC Clinical Translational Research Center (CTRC), the Phase I Program, and the Dept. of Thoracic/Head &amp; Neck Medical Oncology to compare the extent of regulatory and other requirements for current phase I and II cancer clinical trials. Methods: We developed a comprehensive database, together with a Microsoft Excel spreadsheet matrix to analyze the number and extent of diagnostic and therapeutic requirements for each protocol. We then examined the demands for pharmacokinetic (PK) sampling as well as electrocardiography (ECG) in the first cycle of a protocol as a surrogate for study complexity. Results: Since October, 2002, 250 protocols have been conducted in the CTRC; 54.6% were Phase I clinical trials. We reviewed 65 trials, approximately one quarter of the total. Of these, 48 were phase I trials carried out by the Phase I Program. For comparison, we identified 17 phase II trials managed by the Dept. of Thoracic/Head &amp; Neck Medical Oncology during the same time period. In the phase I trials there were significantly more PKs (mean ± SE = 16.69 ± 1.93) than in the phase II trials (mean ± SE = 1.82 ± 1.17) (p&lt;0.0001). Similarly, there were more ECGs in the phase I versus phase II trials (4.46 ± 1.18 vs. 1.41 ± 0.35; p=0.017). Conclusions: Pharmacokinetic collection and ECG monitoring in Phase I trials are complex and labor-intensive. In addition, they represent only a small portion of time-intensive requirements, with increasingly complicated correlates and monitoring (physical exams, imaging, etc.). Successful and accurate Phase I clinical trials require resources and commitment for research infrastructure considerably greater than later phase studies. No significant financial relationships to disclose.
The risk of urinary tract infections in patients with psoriasis on systemic medications in Biobadaderm Registry: A prospective cohort study
Authors: Antonio Sahuquillo-Torralba, Gregorio Carretero, Raquel Rivera, Carlos Ferrándiz, Esteban Daudén-Tello, Pablo de la Cueva, Francisco José Gómez-García, Isabel Belinchón, Enrique Herrera-Acosta, Diana Ruiz-Genao, Marta Ferrán, Mercé Alsina, Jose Luís Sánchez-Carazo, Ofelia Baniandrés, Lourdes Rodríguez Fernández-Freire, Jaime Vilar, Carmen García-Donoso, Jose Manuel Carrascosa, Mar Llamas-Velasco, Enrique Herrera-Ceballos, José Luis López-Estebaranz, Conrad Pujol-Marco, Miguel Ángel Descalzo, Ignacio García-Doval
Journal: Journal of the American Academy of Dermatology (2019)
Retrospective multicentric study on adult intramedullary spinal cord gliomas from a cohort of 319 patients.
Authors: Chantal Campello, fABRICE Parker, Sonia Slimani, Anne Le Floch, Nozar Aghakhani
Journal: Journal of Clinical Oncology (2013)

2068 Background: Intramedullary spinal cord tumors (IMST) are among the rarest types of tumors, account for 2 to 4% of all central nervous system tumors. This study was conducted to describe clinical features, radiological imaging, anatomopathological characteristics, management and outcome of neuroepithelial IMST. Methods: in this retrospective review, a total of 319 patients were included from 7 French neurosurgical University Hospital Centers, between 1984 and 2011. The patient’s pre and postoperative neurological state were classified according to the Mac Cormick scale. Only patients with a preoperative MRI and confirmed histological were included. Results: Mean age at diagnostic was 42.4 for ependymomas, 39.6 for astrocytomas, (included 20 patients older than 65 years old). The male/female ratio was 1.6 for ependymomas, and 1.1 for astrocytomas. Ependymomas were associated with neurofibromatosis in four patients. Pain was the most common presenting symptom (74%), followed by motor (72%), and sensory (66%) complaints. Pre and post operative neurological states were more severe in astrocytomas than ependymomas. The most frequently involved localization was the cervical region for ependymomas, and the thoracic region for astrocytomas. Partial and total resection was achieved in 80% of ependymomas, and 20% of astrocytomas, (diagnostic of other tumors was performed by biopsy). Histological types, according to WHO classification were ependymomas in 72% patients, (94% were low grades), astrocytomas in 24% patiens, (29% were high grades), oligoastrocytomas in 2.4% , and oligodendrogliomas in 1.7%. Postoperative radiotherapy was used especially in high-grade tumors, (67% of ependymomas, 71% of astrocytomas), in absence of severe toxicity. 18% of low-grade astrocytomas received radiotherapy. Chemotherapy was used only in 33% of ependymomas and 24% of astrocytomas. The five-year overall survival rate was 76.8% for astrocytomas, and 94.5% for ependymomas. Conclusions: Histology, preoperative functional score, and grades tumors are confirmed as prognostic factors in this study. Questions about adjuvant therapy for astrocytomas, like intracranial tumors, are answered.
Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis
Authors: Johannes Schneider-Thoma, Orestis Efthimiou, Irene Bighelli, Carola Dörries, Maximilian Huhn, Marc Krause, Leonie Reichelt, Hannah Röder, Toshi A Furukawa, John M Davis, Stefan Leucht
Journal: The Lancet Psychiatry (2019)
Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials
Authors: Borja Ibanez, Anthony H. Aletras, Andrew E. Arai, Hakan Arheden, Jeroen Bax, Colin Berry, Chiara Bucciarelli-Ducci, Pierre Croisille, Erica Dall'Armellina, Rohan Dharmakumar, Ingo Eitel, Rodrigo Fernández-Jiménez, Matthias G. Friedrich, David García-Dorado, Derek J. Hausenloy, Raymond J. Kim, Sebastian Kozerke, Christopher M. Kramer, Michael Salerno, Javier Sánchez-González, Javier Sanz, Valentin Fuster
Journal: Journal of the American College of Cardiology (2019)

After a reperfused myocardial infarction (MI), dynamic tissue changes occur (edema, inflammation, microvascular obstruction, hemorrhage, cardiomyocyte necrosis, and ultimately replacement by fibrosis). The extension and magnitude of these changes contribute to long-term prognosis after MI. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. CMR is also the preferred methodology for the identification of potential benefits associated with new cardioprotective strategies both in experimental and clinical trials. However, there is a wide heterogeneity in CMR methodologies used in experimental and clinical trials, including time of post-MI scan, acquisition protocols, and, more importantly, selection of endpoints. There is a need for standardization of these methodologies to improve the translation into a real clinical benefit. The main objective of this scientific expert panel consensus document is to provide recommendations for CMR endpoint selection in experimental and clinical trials based on pathophysiology and its association with hard outcomes.
Brainstem Circuits Controlling Action Diversification
Authors: Ludwig Ruder, Silvia Arber
Journal: Annual Review of Neuroscience (2019)

Neuronal circuits that regulate movement are distributed throughout the nervous system. The brainstem is an important interface between upper motor centers involved in action planning and circuits in the spinal cord ultimately leading to execution of body movements. Here we focus on recent work using genetic and viral entry points to reveal the identity of functionally dedicated and frequently spatially intermingled brainstem populations essential for action diversification, a general principle conserved throughout evolution. Brainstem circuits with distinct organization and function control skilled forelimb behavior, orofacial movements, and locomotion. They convey regulatory parameters to motor output structures and collaborate in the construction of complex natural motor behaviors. Functionally tuned brainstem neurons for different actions serve as important integrators of synaptic inputs from upstream centers, including the basal ganglia and cortex, to regulate and modulate behavioral function in different contexts.
18F-NaF Uptake in Ocular Prosthesis (Implant)
Authors: Esha Kothekar, Siavash Mehdizadeh Seraj, Fatemeh Kaghazchi, Thomas J. Werner, Abass Alavi
Journal: Clinical Nuclear Medicine (2019)

Abstract Ocular prosthesis is used as a replacement in the orbit following enucleation or evisceration of the eye. Polymethyl methacrylate (PMMA), hydroxyapatite (HA) and porous polyethylene (PP) are some examples of the materials used in ocular prosthesis. We present a case of an 82-year-old man with prostate cancer who underwent 18 F-NaF PET/CT imaging for evaluation of bone metastases and was incidentally found to have increased NaF uptake in the ocular prosthesis.
IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion
Authors: Li-Chuan Chan, Chia-Wei Li, Weiya Xia, Jung-Mao Hsu, Heng-Huan Lee, Jong-Ho Cha, Hung-Ling Wang, Wen-Hao Yang, Er-Yen Yen, Wei-Chao Chang, Zhengyu Zha, Seung-Oe Lim, Yun-Ju Lai, Chunxiao Liu, Jielin Liu, Qiongzhu Dong, Yi Yang, Linlin Sun, Yongkun Wei, Lei Nie, Jennifer L. Hsu, Hui Li, Qinghai Ye, Manal M. Hassan, Hesham M. Amin, Ahmed O. Kaseb, Xin Lin, Shao-Chun Wang, Mien-Chie Hung
Journal: Journal of Clinical Investigation (2019)

Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti-T cell immunoglobulin mucin-3 (anti-Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti-IL-6 and anti-Tim-3 as an effective marker-guided therapeutic strategy.