tbuckley/cabot-search huggingface dataset:
连接蛋白表达的变化与黑色素瘤的 BRAF 突变状态和生存期相关
Journal: British Journal of Dermatology (2022)

Abstract Linked Article: Scatolini et al. Br J Dermatol 2022; 186:117–128. 黑色素瘤是一种严重的皮肤癌, 当皮肤中的色素细胞 (黑素细胞) 出现恶变 (癌变) 时就会发生这种病症。在英国, 每 40 人中约有 1 人患有黑色素瘤。黑色素瘤可扩散到身体其他部位 (即“转移”) , 转移性黑色素瘤是最致命的癌症之一。转移性黑色素瘤中发现了几种突变 (遗传代码中的错误) , 其中包括 BRAF 突变。使用突变 BRAF 抑制剂开发的一种治疗已在对抗黑色素瘤中展现积极进展, 缓解率令人鼓舞。然而, 由于对此类疗法产生耐药性, 寻找其他联合治疗和新的生物标志物以帮助预测哪些患者对不同的治疗有反应仍是一个挑战。 本研究的作者 (来自意大利、日本和英国) 基于自身此前的研究, 此次专注于更好地了解黑色素瘤生物学, 以改善治疗方案并预测患者结局 (他们的预后) 。之前已知一种称为 Connexin 31.1 (或 GJB5) 的间隙连接蛋白在肺癌中发挥作用, 但当前研究的作者已发现转移 (即癌症已扩散) 、BRAF 突变和黑色素瘤中 GJB5 低表达之间存在关联。 本研究强调了监测这种间隙连接蛋白的重要性, 研究表明 GJB5 可作为预测黑色素瘤进展的预后 (结局) 标志物。此外, 作者建议对于未来的研究, GJB5 可能是一个潜在的新治疗靶标, 可以与黑色素瘤的当前疗法联合使用。 Linked Article: Scatolini et al. Br J Dermatol 2022; 186:117–128.
Errors in the Abstract, Key Points, and Text
Authors: Cynthia Fontanella, Guy Brock, Mary Fristad
Journal: JAMA Pediatrics (2021)

Tsung-Chieh Yao, MD, PhD; Jiu-Yao Wang, MD, DPhil; Sheng-Mao Chang, PhD; Yen-Chen Chang, MS; Yi-Fen Tsai, MS; Ann Chen Wu, MD, MPH; Jing-Long Huang, MD; Hui-Ju Tsai, MPH, PhD
Note from the editors: World Health Organization declares novel coronavirus (2019-nCoV) sixth public health emergency of international concern
Journal: Eurosurveillance (2020)

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Effect of fruquintinib on programmed death receptor-1 blockade antitumor immune responses in colorectal cancer.
Authors: Qingli Li, Xiaojiao Cheng, Cong Zhou, Yao Tang, Fuli Li, Baiwen Zhang, Tinglei Huang, Jianzheng Wang, Shuiping Tu
Journal: Journal of Clinical Oncology (2022)

150 Background: Programmed death receptor-1 (PD-1) blockade shows little benefit in the patients with microsatellite-stable colorectal cancer (MSS-CRC).Fruquintinib, a China-made anti-angiogenic drug, applied for third line therapy in mCRC. However, the effects of combination of fruquintinib and PD-1 blockade on MSS-CRC and its relative mechanisms are not well determined. Methods: Syngeneic xenograft mouse models were establish using murine MC38 and CT26 colon cancer cells to assess treatment efficacy. The percentages of immune cells were detected in peripheral blood, spleen and tumor tissues in tumor-bearing mice by flow cytometry analysis. Angiogenesis in tumor tissues was detected by immunofluorescence. The safety of drug treatment was evaluated by histopathology analysis in murine main organs. The efficacy of combination of fruquintinib and sintilimab were verified in the treatment of MSS-CRC patients. Results: Our results showed the combination of fruquintinib and sintilimab exhibited strongest inhibition of tumor growth and achieved longest survival time in mice bearing MC38 or CT26 xenograft tumors, compared to fruquintinib and sintilimab alone. Mechanistically, the combination of fruquintinib and sintilimab reduced angiogenesis, reprogramed the vascular structure, enhanced the infiltration of CD8 + T cells, CD8 + TNFα + T cells and CD8 + IFNγ + T cells and reduced the ratios of MDSCs and macrophages in mice. No obvious damage was observed in main organs in tumor-bearing mice with the combined treatment. Moreover, the treatment of combination of fruquintinib and sintilimab anti-PD-1 antibodies achieved effective response in five refractory advanced MSS CRC patients. Conclusions: Our results show that combination of fruquintinib and sintilimab synergistically inhibits CRC growth by alterating antitumor immune microenvironment.
Transplant coronary artery disease in pediatrics: Favorable outcome with medical therapy Mark M. Boucek, Henry M. Sondheimer, Dunbar Ivy, Elizabeth M. Shaffer, Chris Mashburn, Darcy W. Ripe, Deborah J. Gilbert, Trischa E. Kyle, David N. Campbell, Biagio Pietra. University of Colorado Health Sciences Center/The Children's Hospital, Denver, CO
Journal: Journal of the American College of Cardiology (2001)
Abstract P020: Predictors of Depressive Symptoms Across the Spectrum of Hyperglycemia: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Andreea Rawlings, A. Richey Sharrett, Sherita Golden, B. Gwen Windham, Elizabeth Selvin
Journal: Circulation (2017)

Background: Determinants of depressive symptoms in older adults according to diabetes status have not been widely investigated. Here we examine correlates of depressive symptoms in persons without diabetes, with prediabetes, and with diagnosed diabetes. Methods: We used data from visit 5 (2011-2013) of the ARIC Study. Depressive symptoms were ascertained using the 11-item CES-D, with scores ≥9 indicating probable major depression, and via self-reported diagnosis of depression in the past 2 years. Diabetes was defined based on self-reported diagnosis or use of glucose lowering medication. We defined prediabetes as HbA1c of 5.7-6.4% in persons without diabetes. We examined demographic factors, markers of health status, and metrics of health care access as correlates of depressive symptoms. Prevalence ratios (PRs) were calculated using Poisson regression with robust variance estimation. Results: Among 6319 participants (mean age 76 years, 59% female, and 77% white), the prevalence of depressive symptoms in persons with prediabetes (8.6%) and diabetes (14.7%) was significantly higher than in persons with no diabetes (6.9%). Correlates of depressive symptoms were similar across diabetes categories. In fully adjusted models, the strongest predictors of depressive symptoms were self-reported fair or poor health (compared to excellent health) and variables related to access to, and satisfaction with, health care. In persons with diabetes, insulin use, but not HbA1c control, was significantly associated with depressive symptoms. Measures of socioeconomic status (education, income) were significantly associated with depressive symptoms in all three groups (Table). Conclusions: The strongest predictors of depressive symptoms were metrics of health care access and satisfaction, suggesting that system-level factors may be important in addressing depression in diabetes and prediabetes.
To Transect or Not Transect: Results from the Scandinavian Urethroplasty Study, A Multicentre Randomised Study of Bulbar Urethroplasty Comparing Excision and Primary Anastomosis Versus Buccal Mucosal Grafting
Authors: Ole Jacob Nilsen, Henriette Veiby Holm, Teresa O. Ekerhult, Klas Lindqvist, Beata Grabowska, Beata Persson, Jukka Sairanen
Journal: European Urology (2022)

Open surgical treatment of short bulbar urethral strictures (urethroplasty) is commonly performed as transecting excision and primary anastomosis (tEPA) or buccal mucosa grafting (BMG). Erectile dysfunction and penile complications have been reported, but there is an absence of randomised trials.To evaluate sexual dysfunction and penile complications after urethroplasty with tEPA versus BMG.Centres in Finland, Sweden and Norway participated. Patients with a bulbar urethral stricture of ≤2 cm without previous urethroplasty were randomised. The primary endpoints were the degree of erectile dysfunction and penile complications. Follow-up was 12 mo.Patients were randomised to either tEPA or BMG urethroplasty.Sexual dysfunction was measured using the International Index of Erectile Function, 5-item version (IIEF-5) and a penile complications questionnaire (PCQ) designed for this study. Continuous data were analysed using analysis of covariance and categorical data were compared using a χ2 test.A total of 151 patients were randomised to either tEPA (n = 75) or BMG (n = 76). The tEPA group reported more penile complications (p = 0.02), especially reduced glans filling (p = 0.03) and a shortened penis (p = 0.001). There were no differences in postoperative IIEF-5 total scores. Recurrence rates were similar in both groups (12.9%) but the study was not designed to detect differences in recurrence rates. The PCQ is not validated, which is a limitation.More patients reported penile complications after urethroplasty with tEPA than with BMG. This should be considered when choosing the operative method, and patients should be informed accordingly.This study compared two common operations for repair of narrowing of the male urethra. Neither of the two methods seems to cause worsened erections. However, penile problems are more common after the transection technique than after the grafting technique.
Endoscopic ultrasound- and fluoroscopy-guided jejunojejunostomy with a lumen-apposing metal stent for malignant afferent loop obstruction
Authors: David Jonason, Stuart K. Amateau, Martin L. Freeman, Guru Trikudanathan
Journal: Endoscopy (2022)

A 57-year-old white woman with history of stage IV signet ring cell adenocarcinoma of the ampulla, who had previously undergone a Whipple procedure with Billroth II reconstruction followed by adjuvant chemotherapy, was referred for afferent loop obstruction due to newly diagnosed peritoneal metastatic pancreatic cancer. Small-bowel enteroscopy found a 3-cm segment of extrinsic stenosis near the hepaticojejunostomy, with upstream dilatation. A 10 × 80-mm uncovered self-expanding metal stent (SEMS) was deployed across the stenosis under fluoroscopic guidance ([Fig. 1]). Drainage of bile was immediate; however, within 72 hours, the patient developed cholangitis, with evidence of persistent afferent loop obstruction on repeat computed tomography imaging ([Fig. 2]). After multidisciplinary team discussion, endoscopic ultrasound (EUS)-guided transmural drainage of the dilated afferent loop was pursued ([Video 1]).
Advisory Board and Contents
Authors: Dylan Gee, Ralf Engbert, Maximilian Rabe, Lisa Schwetlick, Stefan Seelig, Sebastian Reich, Shravan Vasishth, Moritz Wurm, Alfonso Caramazza, Daniel Dilks, Frederik Kamps, Andrew Persichetti, Hinze Hogendoorn, Vladislava Segen, Johnson Ying, Erik Morgan, Mark Brandon, Thomas Wolbers, Annemarie Wolff, Nareg Berberian, Mehrshad Golesorkhi, Javier Gomez-Pilar, Federico Zilio, Georg Northoff, Celso De Melo, Antonio Torralba, Leonidas Guibas, James Dicarlo, Rama Chellappa, Jessica Hodgins, Lindsey Drayton, Jessica Miles, Rolf Van Der Sanden, Patrick Scheffmann, Ralph Adolphs, Renee Baillargeon, Nick Chater, Peter Dayan, Stanislas Dehaene, Daniel Dennett, Yadin Dudai, Andreas Engel, Martha Farah, Angela Friederici, Okihide Hikosaka, Ray Jackendoff, Philip Johnson-Laird, Nancy Kanwisher, Christof Koch, Marta Kutas, Nikos Logothetis, James Mcclelland, Earl Miller, Elizabeth Phelps, Russell Poldrack, Marcus Raichle, Trevor Robbins, Anthony Wagner, Vincent Walsh
Journal: Trends in Cognitive Sciences (2022)
Extent of coronary artery calcification in elderly healthy adventist volunteers compared to a healthy aged matched general population David Grout, Bevan Hokin, Kevin Price, Sudheera Nair, Mark Nidorf, Peter L. Thompson, Ross G. T. Walker. Sydney Heart Image of Sydney Adventist Hospital, Sydney, Australia, West Australian Heart Research Institute, Perth, Australia
Journal: Journal of the American College of Cardiology (2001)
Abstract P308: Independent Effects of Individual and Neighborhood Socioeconomic Characteristics on Cardiovascular Health Response to an Exercise Trial
Authors: Candice A Myers, Stephanie T Broyles, Corby K Martin
Journal: Circulation (2018)

Introduction: Both individual-level socioeconomic position (SEP) and the socioeconomic context of neighborhood of residence are important social determinants of cardiovascular health. However, few studies have considered how both individual and neighborhood socioeconomic factors simultaneously impact the effect of an intervention on cardiovascular health. Hypothesis: We assessed the hypothesis that higher individual SEP and lower neighborhood poverty and would each be independently associated with better cardiovascular health in response to the Examination of Mechanisms (E-Mechanic) of Exercise-Induced Weight Compensation randomized control trial. Methods: Cardiovascular health (CVH) was measured via a composite score that included 4 factors (1) BMI, 2) cholesterol, 3) glucose, and 4) systolic blood pressure), each categorized as ideal (2 points), intermediate (1 point), and poor (0 points) health for a possible range of 0 points (worst CVH) to 8 points (best CVH). CVH scores were calculated at baseline and follow-up. Individual SEP was created using principal components analysis with income and educational attainment, controlling for race, to produce a single socioeconomic factor that was dichotomized to indicate high (=1) or low (=0) SEP. Neighborhood socioeconomic context was measured at the census block group using percent (%) poverty derived from the U.S. Census Bureau’s American Community Survey. We estimated a multilevel repeated-measures regression model of CVH against individual SEP and neighborhood poverty that included covariates for age, sex, race, and marital status. Results: The final analytic sample included 114 participants (mean age = 48.3 years, SD age = 11.5 years; 72% female; 30% African American; 72% married) residing in 88 neighborhoods (mean poverty = 14.5%, SD=13.3%) who received the E-Mechanic exercise intervention and who had no missing data for all variables. On average, the E-Mechanic trial improved cardiovascular health among all exercise intervention participants by 0.3 points (95% CI 0.2 to 0.5). Results from the regression model demonstrated that participant SEP only approached marginal significance (p=0.12), while neighborhood poverty was not significant (p=0.32). Conclusions: The current study found that individual and neighborhood socioeconomic characteristics were not independently associated with response in cardiovascular health to the E-Mechanic exercise intervention. While findings from the analysis do not implicate either personal or contextual socioeconomic influences in intervention response for the E-Mechanic trial, this study does address the need to assess potential disparities in randomized control trials by examining differential response in health outcomes among participants by multiple social determinants of health.
Testicular Cancer — Discoveries and Updates
Authors: Xuesong Han, K Yabroff, Anthony Robbins, D Jamal
Journal: New England Journal of Medicine (2014)

notices age (who were eligible for dependent coverage) and those between 26 and 30 years of age (who were not eligible for dependent coverage) had similar demographic characteristics except for level of education and marital status (see Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).After controlling for demographic factors, the receipt of dental checkups, blood-pressure measurement, and routine health checkups significantly increased after the implementation of the dependent-coverage provision in the targeted population of young adults between 19 and 25 years of age, but not in those between the ages of 26 and 30 years.The percentages of persons who received influenza vaccination and Pap testing changed little over this period in both age groups.In differencein-differences analyses comparing changes in the use of these services over time between adults who were between the ages of 19 and 25 years and those who were between the ages of 26 and 30 years, significant changes were observed in the receipt of dental checkups and blood-pressure measurements, but not in the use of the other three services (Fig. 1, and Table S2 in the Supplementary Appendix).We also observed a significant increase (from 36.7% to 42.4%) in the percentage of young adults between the ages of 19 and 25 years who had private dental insurance (Table S1 in the Supplementary Appendix).Although dental checkups are not mandated in dependent coverage under the ACA, many dental-insurance carriers have opted to increase the age limit for dependents in their plans. 5 Although our findings are preliminary, they suggest that modest positive benefits are associated with the ACA legislation to expand dependent coverage.Future studies should continue to monitor access to care and health outcomes in populations who are insured under the ACA.
Research in Brief
Authors: Jennifer Thorley
Journal: The Lancet Rheumatology (2020)

RSLV-132, a biological drug consisting of an RNase–IgG1 Fc fusion protein, improved severe fatigue in patients with primary Sjögren's syndrome in a phase 2 randomised trial. James Posada and colleagues randomly assigned 30 patients (3:1) to receive 10 mg/kg intravenous RSLV-132 (n=22) or placebo (n=8) for 12 weeks. Patients in the RSLV-132 group achieved clinically meaningful improvements on the EULAR Sjögren's syndrome patient reported index (ESSPRI), FACIT fatigue, profile of fatigue, and the digit symbol substitution test, which correlated with increases in interferon-inducible gene expression (the primary outcome) via an unclear mechanism.
SONCAR study: A prospective randomized controlled study on optimized neoadjuvant chemotherapy-oxaliplatin plus CRT in patients with locally advanced rectal cancer.
Authors: Rong-Xin Zhang, Zhifan Zeng, Yuan-Hong Gao, Xiao-Jun Wu, Gong Chen, Liren Li, Pei-Rong Ding, Min Liu, Qiaoxuan Wang, Weiwei Xiao, Zhi-Zhong Pan, De-Sen Wan, Zhen-Hai LU
Journal: Journal of Clinical Oncology (2022)

117 Background: The benefit of adding Oxaliplatin to neoadjuvant chemoradiotherapy in Locally Advanced Rectal Cancer (LARC) patients remains controversial. The present study investigated whether induction chemotherapy (CapOX), 2 cycles of CapOX combined with standard radiation (Oxa-CRT) concurrently and consolidation chemotherapy (CapOX) could improve OS compared with standard treatment (nCRT) for locally advanced rectal cancer. Methods: We conducted this randomized, single center, open-label, phase III trial in China. Eligible patients were pathologically confirmed rectal adenocarcinoma, clinical T3-4 with or without regional N + and no sign of distance metastasis determined by pelvic MRI, chest and abdominal CT scan. All patients were randomly allocated to the experimental group: pelvic radiation of 50Gy/25 fractions with 4 cycles of oxaliplatin and capecitabine (1 cycle of CapOX (oxaliplatin: 130mg/m 2, cape: 1000mg/m 2 , bid, Day 1 to Day 14) administrated before radiotherapy as induction chemotherapy, 2 cycles of CapOX (oxaliplatin: 100mg/m 2 , cape: 1000mg/m 2 , bid, Day 1 to Day 14) administrated concurrent with RT, and 1 cycle of CapOX (oxaliplatin: 130mg/m 2 , cape: 1000mg/m 2 , bid, Day 1 to Day 14) conducted as consolidation chemotherapy); or control group: radiation with capecitabine. The primary end point was OS. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02031939). Results: From January 2014 to June 2020, 556 patients enrolled in this study (n=278 in both groups), and 536 patients were evaluable (269 in experimental group and 267 patients in control group). Surgery was performed in 235 patients (84.5%) in experimental group and 242 patients (87.1%) in control group. The pCR rates were 27.8% (75 in 269) and 19.4% in control group (52 in 267) (p = 0.025). 16 and 5 patients achieved clinical complete response (cCR) in experimental and control group, respectively. Grade 3-4 toxicities were recorded in 42 (21.8%) and 6 (5.1%) patients in experimental and control group. The most common grade 3-4 toxicities were leukopenia, thrombocytopenia and neutropenia. The overall surgical complication rate was not significantly different between two groups (12.1% vs. 11.9%). Conclusions: Four cycles of CapOX combined with RT in LARC significantly increased complete tumor response in Chinese patients with acceptable toxicities. Clinical trial information: NCT02031939.
Impact of the DREAMS Program on New HIV Diagnoses in Adolescent Girls and Young Women Attending Antenatal Care — Lesotho, 2015–2020
Authors: Andrew R. Pelletier, Josip Derado, Limpho Maoela, Thabiso Lekhotsa, Masechache Sechache, Konosoang Nkuatsana
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Lesotho is a small, landlocked country in southern Africa with a population of approximately 2 million persons, approximately two thirds of whom live in rural areas (1). Lesotho has the second highest prevalence of HIV infection in the world (2). In 2017, 25.6% of persons aged 15-59 years living in Lesotho were HIV-positive (3). Strategies implemented in recent years to control HIV include efforts to reduce mother-to-child transmission and improve coverage with antiretroviral therapy, as well as increasing testing for HIV. Among persons aged 15-24 years, the HIV prevalence among females in 2017 (11.1%) was approximately three times that among males (3.4%) (3). The Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS)* program in Lesotho was started during October 2016 in two districts. DREAMS comprises a package of biomedical, behavioral, and structural interventions to address factors that make adolescent girls and young women vulnerable to HIV acquisition (4). The goal of the DREAMS program was to decrease HIV incidence among adolescent girls and young women by 25% after 1 year and by 40% after 2 years (4). After 3.5 years of program implementation in Lesotho, new HIV diagnoses among adolescent girls and young women attending antenatal care (ANC) decreased 71.4% in the two districts that implemented DREAMS compared with a reduction of 48.4% in three comparison districts without the program (p = 0.002). During 2016-2020, reductions in new HIV diagnoses among adolescent girls and young women attending ANC in Lesotho have been substantial, both in districts that have and have not implemented the DREAMS program (DREAMS and non-DREAMS districts). Apart from the DREAMS program, the decrease in new HIV diagnoses might be a result of the reduction in viral load in the population because more persons living with HIV infection became virally suppressed while on antiviral therapy, as well as other interventions such as preexposure prophylaxis, voluntary medical male circumcision, behavior change, and increased HIV diagnostic coverage.