tbuckley/cabot-search huggingface dataset:
NHS agrees to pay £13m for boy who was left brain damaged from lack of nutrition after birth
Authors: Clare Dyer
Journal: BMJ (2021)

The NHS has agreed a settlement totalling £13m for a 15 year old boy who sustained severe brain damage from insufficient nutrition in the days after his birth.1

The boy, referred to as OP in court, was born at the Royal Preston Hospital in 2005 by emergency caesarean section. His mother, who had almost no command of English, wanted to breastfeed him.

Midwifery notes record that he was put to the breast with no apparent problems. But during the second night after his birth, still in the hospital, he became hypoglycaemic as a result of insufficient …
Evaluation of Lymph Node Metastasis Among Adults With Gastric Adenocarcinoma Managed With Total Gastrectomy
Authors: Harbi Khalayleh, Young-Woo Kim, Hong Man Yoon, Keun Won Ryu, Myeong-Cherl Kook
Journal: JAMA Network Open (2021)

<h3>Importance</h3> It is unclear whether proximal gastrectomy (PG) can replace total gastrectomy (TG), even in cases of advanced gastric carcinoma. <h3>Objectives</h3> To evaluate the oncologic safety of PG based on the lymph node (LN) metastasis rate and develop a selection diagram for PG eligibility. <h3>Design, Setting, and Participants</h3> In this cohort study, a retrospective analysis of a prospective database of gastric carcinoma surgery was performed including procedures that took place between December 1, 2000, and December 31, 2015, in the National Cancer Center, Korea, a high-volume carcinoma center with a structured database and accurate long-term follow-up. Among 9952 patients who underwent surgery for gastric carcinoma, 2347 underwent TG. Six-hundred fifty-five (564 in a second statistical analysis) had gastric carcinoma in the upper third of the stomach. The inclusion criteria were age 18 to 85 years, histologically proven adenocarcinoma (any size or differentiation) located in the upper third of the stomach, curative R0 TG performed, and postoperative follow-up for at least 3 years. Exclusion criteria included Borrmann type 4 carcinoma, T4 category, use of neoadjuvant chemotherapy, and a history of other carcinomas. Data analysis was performed from December 1, 2019, to May 30, 2020. <h3>Exposures</h3> Total gastrectomy and LN dissection. <h3>Main Outcomes and Measures</h3> The primary end point was the rate of LN metastasis at LN stations 4d, 5, and 6, which are usually not dissected during PG. <h3>Results</h3> Among the 655 study patients, the mean (SD) age was 57.7 (11.9) years, and 462 (70.5%) were men. Only those with poorly differentiated cT3 category carcinomas had an increased incidence of LN metastasis at stations 4d (2 of 32 [6.3%]) and 11d (T3N0: 2 of 22 [9.1%], T3N1: 3 of 27 [11.1%]), independent of tumor size. For cT1-T3N0/1M0 category carcinomas, the incidence of station 5 LN metastasis was 0, irrespective of tumor size and differentiation. The LN metastasis rate at stations 4d and 6 for cT1-T3N0/1M0 differentiated tumors was also 0. Tumor size greater than or equal to 4.1 cm was associated with significantly increased LN metastasis compared with tumors less than 4.1 cm (40.0% vs 20.4%,<i>P</i> = .001). <h3>Conclusions and Relevance</h3> The findings of this study suggest that PG can be safely performed for cT1-T2N0/1M0 tumors less than 4.1 cm in diameter that are located in the upper third of the stomach. The cT3N0/1M0-differentiated tumors less than 4.1 cm may also be eligible for PG, whereas poorly differentiated cT3 tumors and any cT4 or cN2/3 diseases require TG.
Tuning the efficacy of esterase-activatable prodrug nanoparticles for the treatment of colorectal malignancies
Authors: Yuchen Wang, Haiyang Xie, Kangkang Ying, Binbin Xie, Xiaona Chen, Bing Yang, Jiahui Jin, Jianqin Wan, Tongyu Li, Weidong Han, Shijiang Fang, Hangxiang Wang
Journal: Biomaterials (2021)
Liraglutide Increases the Catabolism of Apolipoprotein B100–Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression
Authors: Bruno Vergès, Laurence Duvillard, Jean Paul Pais de Barros, Benjamin Bouillet, Sabine Baillot-Rudoni, Alexia Rouland, Jean Michel Petit, Pascal Degrace, Laurent Demizieux
Journal: Diabetes Care (2021)

Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins.We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance.In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL1-apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL2-apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver.Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL1, VLDL2, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D.
Incorporating Baseline Breast Density When Screening Women at Average Risk for Breast Cancer
Authors: Ya-Chen Tina Shih, Wenli Dong, Ying Xu, Ruth Etzioni, Yu Shen
Journal: Annals of Internal Medicine (2021)

Breast density classification is largely determined by mammography, making the timing of the first screening mammogram clinically important. To evaluate the cost-effectiveness of breast cancer screening strategies that are stratified by breast density. Microsimulation model to generate the natural history of breast cancer for women with and those without dense breasts and assessment of the cost-effectiveness of strategies tailored to breast density and nontailored strategies. Model parameters from the literature; statistical modeling; and analysis of Surveillance, Epidemiology, and End Results-Medicare data. Women aged 40 years or older. Lifetime. Societal. No screening; biennial or triennial mammography from age 50 to 75 years; annual mammography from age 50 to 75 years for women with dense breasts at age 50 years and biennial or triennial mammography from age 50 to 75 years for those without dense breasts at age 50 years; and annual mammography at age 40 to 75 years for women with dense breasts at age 40 years and biennial or triennial mammography at age 50 to 75 years for those without dense breasts at age 40 years. Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. Baseline screening at age 40 years followed by annual screening at age 40 to 75 years for women with dense breasts and biennial screening at age 50 to 75 years for women without dense breasts was effective and cost-effective, yielding an incremental cost-effectiveness ratio of $36 200 per QALY versus the biennial strategy at age 50 to 75 years. At a societal willingness-to-pay threshold of $100 000 per QALY, the probability that the density-stratified strategy at age 40 years was optimal was 56% compared with 6 other strategies. Findings may not be generalizable outside the United States. The study findings advocate for breast density-stratified screening with baseline mammography at age 40 years. National Cancer Institute.
Yemen: Coronavirus in a War Zone
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

On average, the Saudi-led coalition bombs Yemen 12 times a day. They have been doing so since 2015. It amounts to more than 20 000 air strikes. The north of Yemen is controlled by the Iran-backed Houthis, who conquered the nation's capital Sana'a in September, 2014. The overthrown government, which Saudi Arabia is fighting to restore, has fled the country. It has established a temporary capital in Aden in southern Yemen, though various militias, including ones affiliated with Al Qaeda and Islamic State, are also vying for control.
Biomarkers associated with chronic spontaneous urticaria severity in children
Authors: Lydia Zhang, Michelle Le, Sofianne Gabrielli, Elena Netchiporouk, Luis Felipe Ensina, Shoshana Greenberger, Sharon Baum, Fatemeh Jafarian, Xun Zhang, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2021)
Increased Incidence of IKZF1 deletions and IGH-CRLF2 translocations in B-ALL of Hispanic/Latino children—a novel health disparity
Authors: Gordana Raca, Hisham Abdel-Azim, Feng Yue, James Broach, Jonathon L. Payne, Mark E. Reeves, Chandrika Gowda, Joseph Schramm, Dhimant Desai, Elanora Dovat, Tommy Hu, Arthur S. Berg, Deepa Bhojwani, Kimberly J. Payne, Sinisa Dovat
Journal: Leukemia (2021)
Prediabetes—A Risk Factor Twice Removed
Authors: Kenneth Lam, Sei J. Lee
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Long-Term Safety, Efficacy, and Tolerability of Subcutaneous Human Immunoglobulin 16.5% in Patients with Primary Immunodeficiencies
Authors: Sudhir Gupta, Roger Kobayashi, Isaac Melamed, Syed Rehman, Ai Kobayashi, jose-fernando Mandujano, Bob Geng, Bruce Ritchie
Journal: Journal of Allergy and Clinical Immunology (2021)
Quality of Life After Bladder Cancer: A Cross-sectional Survey of Patient-reported Outcomes
Authors: James W.F. Catto, Amy Downing, Samantha Mason, Penny Wright, Kate Absolom, Sarah Bottomley, Luke Hounsome, Syed Hussain, Mohini Varughese, Caroline Raw, Phil Kelly, Adam W. Glaser
Journal: European Urology (2021)

Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC). To determine this, we undertook a cross-sectional survey covering 10% of the English population. Participants 1–10 yr from diagnosis were identified through national cancer registration data. A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients. Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24. A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non–muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61–74}] vs 85+ yr [84% {95% CI: 81–89}], p = 0.016) and long-term conditions (no conditions [53% {95% CI: 48–58}] vs more than four conditions [94% {95% CI: 90–97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16–25]) than those aged 85+ yr (6.8 [4.5–9.2], p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66–72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48–53], all p < 0.05). HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers. Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.
Abstract IA012: Recent progress with PTEN
Authors: Ramon E. Parsons
Journal: Clinical Cancer Research (2021)

Abstract PTEN is one of the most frequently mutated genes in cancer and is frequently mutated in endometrial carcinoma. Recent progress on PTEN will be presented from our laboratory regarding its role in metabolism, RNA polymerase II transcription, and its expression in tumors with p53 mutations. I) Loss of PTEN activates metabolism of glutamine to pyrimidine and inactivates the ATR DNA damage checkpoint elicited when pyrimidine synthesis is interrupted, which leads to DNA damage and cell death suggesting a metabolic strategy for cancer treatment. II) PTEN in the nucleus binds to RNA polymerase II as wells as CDK7 and CDK9 on chromatin at promoters and regulates RNA Pol II transcription of genes involved in cellular metabolism. Mutation of PTEN increases RNA poly II levels and phosphorylation and increases sensitivity to inhibition of CDK7 and CDK9. III) Mutation of p53 is associated with reduced expression of PTEN and other tumor suppressor genes in many forms of cancer. p53 was found to bind to a dozen tumor suppressor genes in its wild type state and activates their expression under basal low stress conditions when the level of p53 is at a low level. All of these tumor suppressor genes had p53 binding elements in their promoters and enhancers and deletion of the element in a PTEN enhancer lowered its expression. These findings suggest that p53 mediates tumor suppression by maintaining the expression of other tumor suppressor genes including PTEN. Citation Format: Ramon E. Parsons. Recent progress with PTEN [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA012.
Abstract PO018: PAX8 represents a potential novel therapeutic target in copy number high uterine serous carcinoma
Authors: Susan H. Read, Matthew L. Anderson, Thomas J. Rutherford, Venkata A. Jonnalagadda, Yongchao Dou, Bing Zhang
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Assess the suitability of PAX8 as a therapeutic target in copy number (CNV)-high uterine cancers. Methods: Patterns of gene expression and somatic mutations were evaluated across 97 specimens of uterine cancers characterized by the National Institute of Health’s Clinical Proteomics Tumor Analysis Consortium. Three established USC cell lines (ARK1, ARK2, ARK4) were transfected with small interfering RNAs (siRNAs) targeting PAX8 or a non-targeting siRNA control. Proliferation and apoptosis were evaluated using MTS and Caspase 3/7 assays, respectively. Migration and invasion were evaluated using Boyden chamber assays. PAX8 expression was evaluated using semi-quantitative rtPCR and Western blot. Statistical significance was evaluated using two-tailed t-tests. Results: Our analyses revealed that PAX8 is highly expressed in a subset of uterine cancers and correlates with advanced clinical stage, serous histology and inactivating TP53 mutations. In vitro, knockdown of PAX8 expression resulted in significantly decreased rates of proliferation and apoptosis when compared to cells transfected with non-targeting controls. Decreased proliferation was seen most profoundly at the 72- and 96-hour time points. Enforced reductions in PAX8 expression also decreased rates of tumor migration and invasion. Invasion was significantly decreased in ARK1 (p = 0.05). Migration was significantly decreased in ARK2 (p = 0.002), and the decrease in invasion approached statistical significance (p=0.07). In ARK4, both migration (p = 0.02) and invasion (p = 0.02) were significantly decreased. Knockdown of PAX8 was confirmed using rtPCR for all in vitro experiments. Conclusion: High levels of PAX8 expression are a key feature of a CNV-high uterine cancers that drive tumor proliferation, invasion and migration. These results indicate that PAX8 overexpression contributes to the aggressive clinical behavior of these cancers. They also establish that agents targeting PAX8 activity or expression could ultimately prove to be effective therapeutically. Citation Format: Susan H. Read, Matthew L. Anderson, Thomas J. Rutherford, Venkata A. Jonnalagadda, Yongchao Dou, Bing Zhang. PAX8 represents a potential novel therapeutic target in copy number high uterine serous carcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO018.
Abstract 45: Incomplete Kawasaki Disease followed by Systemic Onset Juvenile Idiopathic Arthritis
Authors: Jeong-hyun Jo, Na-yeon Kim, Eell Ryoo
Journal: Circulation (2015)

Incomplete Kawasaki disease (KD) is second most common systemic vasculitis presented with persistent fever in childhood. Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare rheumatic arthritis characterized with spiking fever for more than 6 weeks with prominent painful joint swelling. KD may trigger or prodrome of SoJIA. Both diseases have overlapping clinical features and laboratory findings including fever, rash, lymphadenitis, thrombocytosis, arthralgia and coronary artery dilatation so that they could hardly be distinguished. We present 4 years old girl and 30 months old girl who presented with persistent fever, rash and arthralgia. They were initially diagnosed with incomplete KD and treated with intravenous immunoglobulin and steroids. Spiking fever and painful swelling of bilateral knee joints were noticed after 25days and 40days of illness. They were diagnosed with SoJIA followed by incomplete KD and treated with NSAIDs and MTX in addition. Neither coronary complication nor joint complication was noticed. Careful follow up is needed for patients with KD and arthralgia.
COVID‐19 infection in patients with connective tissue disease: A multicity study in Hubei province, China
Authors: Cong Ye, Jixin Zhong, Shaozhe Cai, Li Dong, Chuanjing Li, Xiaoqiang Hou, Xiaoqi Chen, Anbing Zhang, Wenli Chen, Dongchu He, Tao Zhou, Guilian Shang, Aichun Chu, Huiling Li, Qihuan Liu, Bin Wu, Xiangdong Yu, Tao Peng, Cheng Wen, Gang Hong Huang, Hao Huang, Qin Huang, Linchong Su, Wenping Chen, Huiqin Yang, Lingli Dong
Journal: MedComm (2021)

Abstract Novel Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID‐19 patients hospitalized in 23 centers affiliated to Hubei COVID‐19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID‐19 infection ( p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts ( p values were 0.033, &lt; 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low‐ to medium‐dose glucocorticoids before COVID‐19 diagnosis reduced the progression of COVID‐19 to severe/critical conditions ( p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID‐19 in CTD patients may be more severe compared to patients with AS or gout.
The cancer metabolic reprogramming and immune response
Authors: Longzheng Xia, Linda Oyang, Jinguan Lin, Shiming Tan, Yaqian Han, Nayiyuan Wu, Pin Yi, Lu Tang, Qing Pan, Shan Rao, Jiaxin Liang, Yanyan Tang, Min Su, Xia Luo, Yiqing Yang, Yingrui Shi, Hui Wang, Yujuan Zhou, Qianjin Liao
Journal: Molecular Cancer (2021)

The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.
Development of a Novel, Interactive, Electronic Pediatric Asthma Diary for Self-Report of Symptom Severity and Disease Impact by Young Children With Asthma
Authors: Marci Clark, Carla Romano, Oyebimpe Olayinka-Amao, Diane Whalley, Rebecca Crawford, Purnima Pathak, Caterina Brindicci, Kristin Garg, Kattayoun Kordy, Francois Everhard, Francesco Patalano, Zach Roesler, Thomas Sutton, Oskar Goransson, Ross Landles, Christel Naujoks, Jessica Marvel, Dorothy Keininger
Journal: Journal of Allergy and Clinical Immunology (2021)