tbuckley/cabot-search huggingface dataset:
Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference
Authors: Andrew S. Levey, Kai-Uwe Eckardt, Nijsje M. Dorman, Stacy L. Christiansen, Ewout J. Hoorn, Julie R. Ingelfinger, Lesley A. Inker, Adeera Levin, Rajnish Mehrotra, Paul M. Palevsky, Mark A. Perazella, Allison Tong, Susan J. Allison, Detlef Bockenhauer, Josephine P. Briggs, Jonathan S. Bromberg, Andrew Davenport, Harold I. Feldman, Denis Fouque, Ron T. Gansevoort, John S. Gill, Eddie L. Greene, Brenda R. Hemmelgarn, Matthias Kretzler, Mark Lambie, Pascale H. Lane, Joseph Laycock, Shari E. Leventhal, Michael Mittelman, Patricia Morrissey, Marlies Ostermann, Lesley Rees, Pierre Ronco, Franz Schaefer, Jennifer St. Clair Russell, Caroline Vinck, Stephen B. Walsh, Daniel E. Weiner, Michael Cheung, Michel Jadoul, Wolfgang C. Winkelmayer
Journal: Kidney International (2020)

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.
GABA neurons in the nucleus tractus solitarius express GLP-1 receptors and mediate anorectic effects of liraglutide in rats
Authors: Samantha M. Fortin, Rachele K. Lipsky, Rinzin Lhamo, Jack Chen, Eun Kim, Tito Borner, Heath D. Schmidt, Matthew R. Hayes
Journal: Science Translational Medicine (2020)

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is approved for the treatment of obesity; however, there is still much to be learned regarding the neuronal sites of action that underlie its suppressive effects on food intake and body weight. Peripherally administered liraglutide in rats acts in part through central GLP-1Rs in both the hypothalamus and the hindbrain. Here, we extend findings supporting a role for hindbrain GLP-1Rs in mediating the anorectic effects of liraglutide in male rats. To dissociate the contribution of GLP-1Rs in the area postrema (AP) and the nucleus tractus solitarius (NTS), we examined the effects of liraglutide in both NTS AAV-shRNA-driven
重症下肢虚血の患者に対するアンギオソームコンセプトに基づく血管間療法後の1年間転帰 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Nishijima Tsunenori, Morihisa Kenji, Ono Takamichi, Kugimiya Fumihito, Fukushima Hironobu, Sumida Hitoshi, Noda Katsuo, Ohshima Shuichi
Journal: Circulation (2013)
Predicting and monitoring tumor response to epidermal growth factor receptor inhibitor gefitinib in patients with locally advanced esophageal adenocarcinoma
Authors: M. K. Gibson, H. Mezzadra, L. Kleinberg, S. Jagannath, M. Brock, N. Abdallah, M. Rudek, D. Berman, A. Forastiere, S. Altiok
Journal: Journal of Clinical Oncology (2007)

14112 Background: This study aimed to validate an ex vivo chemosensitivity assay to measure the pharmacodynamic effect of gefitinib on esophageal adenocarcinoma (EAC) prior to treatment with pre-operative concomitant chemoradiotherapy (CRT). Methods: A 14 day run-in period with 250 mg/day of gefitinib preceded CRT. Endoscopic biopsies (D 0 and 14) in 4 patients with T 2–3 N 0/1 M 0/1a EAC were analyzed by ex vivo chemosensitivity assay. Day 0 tissue was exposed to gefitinib ex vivo, then tumor was exposed to gefitinib for 14 days in vivo (ie in the patient). Phosphorylation of the EGFR, raf/MEK/ERK and PI3/AKT pathways was measured by Western blot. Profiles were compared for correlation between ex vivo and in vivo exposure, and patterns were correlated with response to CRT. The effects were also characterized by immunohistochemistry (IHC). EGFR, K-Ras, and PI3K mutations, serum concentrations of gefitinib and PTEN status were measured as potential confounders. Results: One patient with stage T3N1 died of unexplained hemorrhage during surgery. Three had clinical and path stages of: T3N1/T0N0, T3N0/T3N0, T3N1/T2N1. Gefitinib levels were constant, confirming exposure of target tissue to the drug. Ex vivo exposure yielded four distinct pathway patterns. The exact same patterns were seen after in vivo exposure. No mutations were identified in exons 18–21 of the EGFR, exons 2/3 of K-ras or exons 9/22 of PI3K. PTEN levels were similar in all tumors. PCNA expression correlated with raf/MEK/ERK pathway inhibition, but not with inhibition of EGFR activity. IHC correlated with Western blot for expression of EGFR, and phospho- and total ERK levels. No correlation was observed between gefitinib effect and pathologic response to CRT. Conclusions: This study used a novel ex vivo chemosensitivity assay to demonstrate the activity of gefitinib to inhibit target in tumor tissue obtained from patients with EAC. The exact correlation of pre- and post-treatment profiles suggests potential use in the pre-treatment setting to predict in vivo effects of targeted therapies. This approach may facilitate the further refinement of patient selection to maximize potential benefit while sparing patients unlikely to respond to a given agent. No significant financial relationships to disclose.
Homogeneous MMR Deficiency Throughout the Entire Tumor Mass Occurs in a Subset of Colorectal Neuroendocrine Carcinomas
Authors: Christoph Fraune, Ronald Simon, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Martina Kluth, Franziska Büscheck, Tania Amin, Fabrice Viol, Wilfrid Fehrle, David Dum, Doris Höflmayer, Eike Burandt, Till Sebastian Clauditz, Daniel Perez, Jakob Izbicki, Waldemar Wilczak, Guido Sauter, Stefan Steurer, Jörg Schrader
Journal: Endocrine Pathology (2020)

Abstract Neuroendocrine neoplasms comprise a heterogeneous group of tumors, categorized into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) depending on tumor differentiation. NECs and high-grade NETs (G3) confer a poor prognosis, demanding novel treatment strategies such as immune checkpoint inhibition in tumors with microsatellite instability (MSI). To study any possible intratumoral heterogeneity of MSI, a tissue microarray (TMA) containing 199 NETs and 40 NECs was constructed to screen for MSI using immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. Four cases suspicious for MSI were identified. Validation of MSI by repeated IHC on large sections and polymerase chain reaction (PCR)–based analysis using the “Bethesda Panel” confirmed MSI in 3 cecal NECs. One pancreatic NET G3 with MSI-compatible TMA results was MMR intact on large section IHC and microsatellite stable (MSS). The remaining 235 tumors exhibited intact MMR. Protein loss of MLH1/PMS2 was found in two and MSH6 loss in one cancer with MSI. Large section IHC on all available tumor-containing tissue blocks in NECs with MSI did not identify aberrant tumor areas with intact MMR. Our data indicate that MSI is common in colorectal NECs (3 out of 10) but highly infrequent in neuroendocrine neoplasms from many other sites. The lack of intratumoral heterogeneity of MMR deficiency suggests early development of MSI during tumorigenesis in a subset of colorectal NECs and indicates that microsatellite status obtained from small biopsies may be representative for the entire cancer mass.
Abstract P125: Interaction Effects of Diabetes and Subclinical Hypothyroidism on Heart Rate Variability. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Rosangela Hoshi, Itamar S Santos, Eduardo Dantas, Rodrigo Andreao, Bruce Duncan, Maria Schmidt, Jose-Geraldo Mill, Paulo A LOTUFO, Isabela M Bensenor
Journal: Circulation (2020)

Background: Diabetes and subclinical hypothyroidism are frequently coexisting conditions. The separated effects of each one on the cardiovascular system and cardio autonomic function are known. However, it has not been investigated yet whether the presence of both diseases has a joint influence on the cardiac autonomic system. As the autonomic nervous system is involved in cardiovascular, endocrine, and metabolic control, the association of diabetes and subclinical hypothyroidism might have combined effects, leading to cardio autonomic impairment and rising cardiovascular risk. Aim: To analyze the interaction effects of diabetes and subclinical hypothyroidism on Heart Rate Variability parameters among adults. using the participants enrolled at the baseline data of t Methods: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort of 15015 men and women aged 35 to 74 years-old recruited in 2008-10. Participants were categorized into four groups: non-diabetes with normal thyroid function (controls), non-diabetes with subclinical hypothyroidism; diabetes with normal thyroid function; and diabetes with subclinical hypothyroidism. Heart Rate Variability analyses were performed in time and frequency domains: Standard Deviation of NN interval (SDNN); Root of the Mean of the Sum of the Squares of Differences between adjacent NN intervals (RMSSD, Low-Frequency (LF) and High-Frequency (HF) on 5-minute time series collected in the supine position. For each Heart Rate Variability parameter, we divided the sample into quartile groups, using the fourth quartile as reference. We analyzed the associations with the highest quartile group for each Heart Rate Variability parameter using additive and multiplicative terms in logistic models. Results: Point Odds Ratio, and 95% Confidence Intervals (95%CI) estimates for the first quartiles of all Heart Rate Variability measures were higher for subjects with the combination of both, “diabetes plus subclinical hypothyroidism” than for people with only the diagnosis of diabetes: SDNN: 2.61 (95%CI = 1.13 to 6.05) vs. 1.52 (95%CI =1.25 to 1.85); RMSSD: 2.70 (95%CI =1.18 to 6.18) vs. 1.48 (95%CI =1.21 to 1.80); LF: 2.82 (95%CI =1.05 to 7.56) vs. 1.73 (95%CI =1.40 to 2.13); HF: 3.07 (95%CI =1.21 to 7.75) vs. 1.41 (95%CI =1.16 to 1.71). Nonetheless, no significant multiplicative interaction terms between diabetes and subclinical hypothyroidism were found for the association with HRV variables. Conclusion: There is a potential joint impact on Heart Rate Variability showed by additive effects between diabetes and subclinical hypothyroidism.
Association of Late-Onset Unprovoked Seizures of Unknown Etiology With the Risk of Developing Dementia in Older Veterans
Authors: Ophir Keret, Tina D. Hoang, Feng Xia, Howard J. Rosen, Kristine Yaffe
Journal: JAMA Neurology (2020)

The incidence of unprovoked seizures and epilepsy increases considerably in late life, with approximately one-third of seizures being of unknown etiology. While individuals with dementia have a high risk of developing unprovoked seizures, it is unknown whether older adults with late-onset unprovoked seizures of unknown etiology (LOSU) are at risk of developing dementia.To determine whether incident LOSU is associated with a higher risk of dementia among older US veterans.This retrospective multicenter cohort study was conducted using data from US Veterans Health Administration medical centers from October 2001 to September 2015. Data were generated from all veteran inpatient and outpatient encounters that occurred within Veterans Health Administration facilities. A random sample of 941 524 veterans 55 years and older was generated. A total of 649 262 veterans previously diagnosed (using International Classification of Diseases, Ninth Revision, Clinical Modification codes) with dementia, unprovoked seizures, epilepsy, and conditions that could lead to seizures (brain tumors, trauma, infections, stroke, and neurotoxin exposure) as well as veterans without follow-up data were excluded. Data were analyzed from October 2018 to July 2019.Late-onset unprovoked seizures of unknown etiology were defined as a new diagnosis of epilepsy or unprovoked seizures without a diagnosis of a secondary cause for seizures. Incident LOSU was assessed during a 5-year baseline period.Veterans were assessed for incident dementia diagnosis during an outcome period. Fine-Gray proportional hazards models were used to determine whether LOSU was associated with greater risk of incident dementia. Models were adjusted for demographic variables, cardiovascular risk factors, depression, and traumatic brain injury.Of the 292 262 included veterans, 282 628 (96.7%) were male, and the mean (SD) age was 73.0 [8.8] years. During the baseline period, 2166 veterans developed LOSU. The mean (SD) follow-up after LOSU was 6.1 (2.9) years. After multivariable adjustment, veterans with LOSU had greater risk of dementia compared with veterans without seizures (hazard ratio, 1.89; 95% CI, 1.62-2.20). A sensitivity analysis imposing a 2-year lag between incident LOSU and dementia diagnosis led to similar results.These findings suggest LOSU in older veterans is associated with a 2-fold risk of developing dementia. While seizures are commonly thought to occur in late stages of dementia, these findings suggest unexplained seizures in older adults may be a first sign of neurodegenerative disease.
Do 2019 European League against rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus also indicate the disease activity?
Authors: Jialin Teng, Zhuochao Zhou, Fan Wang, Yue Sun, Hong-Lei Liu, Xiaobing Cheng, Yutong Su, Hui Shi, Chengde Yang, Junna Ye
Journal: Annals of the Rheumatic Diseases (2020)

Table 1 The clinical characteristics of new-onset SLE patients diagnosed with 2019 criteria Clinical criteriaPositive/total patients (%)
Exercise capacity and quality of life late after Fontan surgery.
Authors: Yves D'Udekem, Michael H Cheung, Stella Setyapranata, Ajay J Iyengar, Melissa Newton, Patricia Kelly, Naomi Buckland, Leeanne Grigg, Robert G Weintraub, Andrew D Cochrane, Alasdair Vance, Christian P Brizard, Dan J Penny
Journal: Circulation (2007)
Covid-19: UK trade talks with EU must not hinder cooperation in tackling threat, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2020)

A post-Brexit trade agreement between the UK and the European Union must maximise cooperation to ensure that pandemic threats such as covid-19 can be tackled effectively, the BMA has said.

The BMA’s chair of council, Chaand Nagpaul, said in a letter to the UK prime minister, Boris Johnson, that any agreement must not reduce the ability of UK organisations and the European Centre for Disease Prevention and Control to cooperate for the benefit of patients.

Nagpaul acknowledged Johnson’s statement that the comprehensive …
Managing multimorbidity: all doctors started as generalists
Authors: Hamish Duncan
Journal: BMJ (2020)

Gandhi provides a fitting warning of the dangers facing a specialised NHS: “The expert knows more and more about less and less until he knows everything about nothing.”

This will be obvious to any junior doctor of the past 30 years. I have seen a cardiology patient with stable asthma being delayed at discharge for an unnecessary respiratory review; inpatients with conjunctivitis having an ophthalmology review …
Erratum. Who Is Enrolling? The Path to Monitoring in Type 1 Diabetes TrialNet’s Pathway to Prevention. Diabetes Care 2019;42:2228–2236
Authors: Emily K. Sims, Susan Geyer, Suzanne Bennett Johnson, Ingrid Libman, Laura M. Jacobsen, David Boulware, Lisa E. Rafkin, Della Matheson, Mark A. Atkinson, Henry Rodriguez, Maria Spall, Helena Elding Larsson, Diane K. Wherrett, Carla J. Greenbaum, Jeffrey Krischer, Linda A. DiMeglio
Journal: Diabetes Care (2020)

A committee was inadvertently omitted from the list of Type 1 Diabetes TrialNet Study Group …
Expression profiles can predict specific responses of capecitabine/docetaxel (C/D) based primary systemic therapy in breast cancer (BC) patients receiving neoadjuvant therapy
Authors: C. Perou, C. Moisa, S. Gulick, D. Tripathy
Journal: Journal of Clinical Oncology (2007)

587 Background: The identification of efficacious neoadjuvant chemotherapy for BC is critical, especially if regimens with good activity and fewer side effects can be identified. Methods: This open-label, multicenter study of C 825 mg/m 2 twice daily d1–14 plus D 75 mg/m 2 every 21d for 4 cycles for HER2-neu negative (HER2-) patients (pts), and combined with trastuzumab (T) 4 mg/kg loading dose then 2 mg/kg qw for HER2-neu positive (HER2+) pts as preoperative therapy for newly diagnosed BC T2 N1 and T3 N1 (stages II and III), has enrolled 112 pts. The study aims to determine the activity of C+D±T as primary systemic neoadjuvant therapy for operable BC and to identify potential biomarkers of response. The primary endpoint is pathological complete response, with secondary endpoints including clinical response rates after 2 and 4 cycles. Ninety-nine HER2- and 38 HER2+ pts will be recruited and evaluated for gene expression patterns, p53 mutation status, and circulating tumor cells. Results: The interim analysis for the first 30 HER2- pts shows an overall clinical response rate of 83.3% (tumor size reduction 55.5%), and 84.5% for 13 HER2+ pts (tumor size reduction 61.8%). Characteristics of 38 HER2- pts: mean age 51.9y; white 73.7%, African American (AA) 10.5%; premenopausal 36.8%, post 60.5%; ductal 86.8%, lobular 7.9%; ER+ 63.2%, ER- 36.8%. For 16 HER2+ pts: mean age 56y; white 75.0%, AA 12.5%; premenopausal 25.0%, post 75.0%; ductal 93.8%, lobular 6.3%; ER+ 43.8%, ER- 56.3%. The gene expression data (n=50) identifies tumors of all “intrinsic subtypes” and shows a potentially statistically significant association between pathological and clinical response and the HER2+/ER- subtype. Conclusions: Four cycles of C+D+T is active for HER2+ and HER 2- pts prior to surgery. Confirmation of these early results will likely require the entire study sample set. Genomic analyses continue to be conducted on pretherapy tissue samples. [Table: see text]
Dextromethorphan-Quinidine for Agitation in Alzheimer Disease RESPONSE
Authors: JC Newman, MA Steinman
Journal: JAMA (2016)

Letter re: Dextromethorphan-Quinidine for Agitation in Alzheimer Disease. To the Editor: Behavioral complications of dementia can be highly distressing, and new interventions to treat this condition are needed. However, several aspects of the trial on the effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia by Dr Cummings and colleagues caused us concern 1 . First, the increase in falls associated with use of dextromethorphan-quinidine (8.6% vs 3.9% for placebo) was substantial and calls into question the conclusion that the drug was “generally well tolerated.” Although the finding of excess falls may be due to chance or an imbalance in baseline characteristics between the intervention and control groups, this effect should be presumed real until proven otherwise. This interpretation is supported by previous randomized trials of dextromethorphan-quinidine for pseudobulbar affect, in which rates of dizziness were consistently and markedly higher in the active treatment group, although data on falls were conflicting 2-4 . Second, we have concerns about the patenting and use of proprietary study designs in research, such as the Trimentum methodology (a form of crossover study design) used in the study. Regardless of the merits of the methodology, the study cannot be replicated as performed without license from the patent holders. This gives the patent holders a veto over the replication of this particular study and indeed over any validation of the methodology in general. Patented study designs violate the long-cherished principle that scientific findings must be able to be readily reproduced by an independent party. Moreover, allegations of patent infringement and the
Integrin β1D Deficiency–Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Yihui Wang, Chunyan Li, Ling Shi, Xiuyu Chen, Chen Cui, Jinhua Huang, Biyi Chen, Duane D. Hall, Zhenwei Pan, Minjie Lu, Jiang Hong, Long-Sheng Song, Shihua Zhao
Journal: Circulation (2020)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood.Using protein mass spectrometry analyses, we identified that integrin β1 is downregulated in ARVC hearts without changes to Ca2+-handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin β1D loss on function in the heart in vivo and in vitro.Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, β1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca2+ handling in β1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin β1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal-regulated kinase 1 and 2)-fibronectin-ubiquitin/lysosome pathway.Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.