tbuckley/cabot-search huggingface dataset:
Clinical Management of Congenital Hypogonadotropic Hypogonadism
Authors: Jacques Young, Cheng Xu, Georgios E Papadakis, James S Acierno, Luigi Maione, Johanna Hietamäki, Taneli Raivio, Nelly Pitteloud
Journal: Endocrine Reviews (2019)

The initiation and maintenance of reproductive capacity in humans is dependent on pulsatile secretion of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with mutations in >30 genes identified to date acting either alone or in combination. CHH can be challenging to diagnose, particularly in early adolescence where the clinical picture mirrors that of constitutional delay of growth and puberty. Timely diagnosis and treatment will induce puberty, leading to improved sexual, bone, metabolic, and psychological health. In most cases, patients require lifelong treatment, yet a notable portion of male patients (∼10% to 20%) exhibit a spontaneous recovery of their reproductive function. Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients. In summary, this review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development.
Liposomal dexamethasone inhibits tumor growth in an advanced human-mouse hybrid model of multiple myeloma
Authors: Anil K. Deshantri, Marcel H. Fens, Ruud W.J. Ruiter, Josbert M. Metselaar, Gert Storm, Louis van Bloois, Aida Varela-Moreira, Sanjay N. Mandhane, Tuna Mutis, Anton C.M. Martens, Richard W.J. Groen, Raymond M. Schiffelers
Journal: Journal of Controlled Release (2019)
A Phase II Study of Brentuximab Vedotin (BV) in the Treatment of Elderly Hodgkin Lymphoma (HL) Patients at First Relapse or with Primary Refractory Disease — FIL_BVHD01
Authors: Lorenzo Tonialini, Vittorio Stefoni, Alessandro Re, Arben Lleshi, Maurizio Bonfichi, Antonello Pinto, Nicola Bianchetti, Lisa Argnani, Pier Luigi Zinzani
Journal: Blood (2018)
A Murine Model Of Asthma That Replicates The Human Asthma Puberty Switch
Authors: Sergio E. Chiarella, Lyda Cuervo-Pardo, Mackenzie E. Coden, Ton C. Doan, Raul I. Rodriguez, Brian M. Jeong, Sergejs Berdnikovs
Journal: Journal of Allergy and Clinical Immunology (2019)
Exercise influence on the microbiome–gut–brain axis
Authors: Alyssa Dalton, Christine Mermier, Micah Zuhl
Journal: Gut Microbes (2019)

The microbiome in the gut is a diverse environment, housing the majority of our bacterial microbes. This microecosystem has a symbiotic relationship with the surrounding multicellular organism, and a balance and diversity of specific phyla of bacteria support general health. When gut bacteria diversity diminishes, there are systemic consequences, such as gastrointestinal and psychological distress. This pathway of communication is known as the microbiome–gut–brain axis. Interventions such as probiotic supplementation that influence microbiome also improve both gut and brain disorders. Recent evidence suggests that aerobic exercise improves the diversity and abundance of genera from the Firmcutes phylum, which may be the link between the positive effects of exercise on the gut and brain. The purpose of this review is to explain the complex communication pathway of the microbiome–gut–brain axis and further examine the role of exercise on influencing this communication highway.
Doctors to get real time data to support antibiotic prescribing and reduce resistance
Authors: Susan Mayor
Journal: BMJ (2019)

The UK government’s five year national action plan on antimicrobial resistance,1 published this week, aims to strengthen antibiotic stewardship by providing prescribers with real time data on patient level prescribing and resistance during consultations.

“The threat of antimicrobial resistance cannot be overstated. Without intervention, it is not an exaggeration to say that we could return to the dark ages of medicine,” said the chief medical officer for England, Sally Davies. “Too many people are already dying as a result of drug resistant infections around the world, while many still do not have access to the antibiotics they need.”

The plan sets targets of reducing the use of antibiotics in humans in the UK by 15% by 2025 …
The power of norms to sway fused group members
Authors: Winnifred R. Louis, Craig McGarty, Emma F. Thomas, Catherine E. Amiot, Fathali M. Moghaddam
Journal: Behavioral and Brain Sciences (2018)

Abstract Whitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.
Abstract 70: Characterization of Advanced Glycation End Products in a Myocardial Infarction Animal Model
Authors: Bianca Fracasso, Juliana O Rangel, Virgílio Olsen, Amanda Phaelante, Fernanda Curuja, Amanda Lopes, Luis E Rohde, Andreia Biolo, Michael Andrades
Journal: Circulation Research (2016)

Advanced glycation end products (AGE) are molecules produced by oxidative and inflammatory metabolism. Studies have shown that increased AGE levels worse the prognosis of the cardiovascular diseases. However, there is no characterization of AGE generation in a representative animal model of myocardial infarction (MI). Thus, our goal was to characterize the AGE formation in plasma and cardiac tissue in an animal model of MI. Male Wistar rats (3 month-old) were divided in 2 groups: Sham (n = 15) and MI (n = 14) and followed by 12 week. MI was induced by left anterior descending coronary artery (LAD) permanent ligation and the animals were stratified in 2 groups according to ejection fraction (EF) median at 2 days post-MI. MI induced 47% and 29% increase in heart weight/final body weight ratio in MIlowEF MIhighEF group, respectively. There was no significant difference among the groups in the plasma levels of reactive free amines, fluorescents AGE, Nε-(Carboxymethyl)lysine (CML) and Nε-(Carboxyethyl)lysine (CEL) in a 12-week follow-up. However, a significant decrease in the levels of yellowish-brown colored AGEs was revealed in MIlowEF group when compared to Sham. In the cardiac tissue homogenate there was no difference in the amounts of reactive free amines and carbonyl protein among the groups. Our results suggest that a widely employed animal model of MI partially agrees with the human manifestation of the ischemic heart disease concerning the AGEs metabolism. Thus, its use must be employed with caution when studying AGEs signaling or anti-AGE drugs.
Abstract P3-03-43: Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer
Authors: H Yang, S Wang, D Shen, Y Cao, F Tong, D Chen, P Liu, Y Peng
Journal: Cancer Research (2019)

Abstract Background and Objectives: Although de-escalation of axillary surgery becomes more popular, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node(SLN) positive patients not meeting the criteria of ACOSOG Z0011 in many hospitals, and frozen section (FS) of SLN is one of the valuble intra-operative assesments to avoid axilla re-operation although it was controversial due to accuracy and efficiency concerns. This study was to assess the performance of selective use of frozen section evaluation guided by MSKCC lymph node metastasis risk prediction nomogram to optimize the proceudure to be more accurate and cost effective. Methods: Surgical pathology records of consecutive 2582 biopsies in 2552 patients breast cancer patients from 2011 to 2017 were reviewed, intra-operative frozen section diagnosis were compared to post-operative paraffin reports. We calculated the sensitivity, specificity, accuracy and FNR for different MSKCC risk, the axilla re-operation rate with or without FS and the number needed to treat (NNT) to avoid second ALND was also analyzed. Results: The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3% respectively. The axilla re-operation rates were significantly decreased if FS was done(4.7%±0.4% with FS versus 35.8%±5.8% without FS, P&amp;lt;0.001). The estimated axilla re-operation rate without FS was positively correlated with MSKCC risk(r=0.99, P&amp;lt;0.001), while NNT to avoid second ALND by FS were negatively correlated with MSKCC risk(r=-0.98, P&amp;lt;0.001). When patients were divided into four groups according to quartile MSKCC risk, the axilla re-excisional rates were 18.4%, 25.1%, 38.7%, 58.7% without FS, while 4.8%, 3.2%, 5.6%, 3.2% with FS, and NNT correspondingly decreased from 7.3, 4.5, 3.0 to 1.8. An decision-making algorithm for application of FS was proposed. Conclusion: Stratified decision-making algorithm based on MSKCC prediction model improved the efficiency of FS to avoid axilla re-operatioin in patients undergoing sentinel lymph node biopsy. We recommend FS be restricted to patients with MSKCC risk higher than 0.5 who do not meet ACOSOG Z0011 criteria. Citation Format: Yang H, Wang S, Shen D, Cao Y, Tong F, Chen D, Liu P, Peng Y. Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-43.
Unravelling Genetic Mechanisms of Erythrocytosis: A Real-Life Experience from a Single Center
Authors: Carmelo Gurnari, Annamaria Lombardi, Elisabetta Cosi, Giacomo Biagetti, Francesco Buccisano, Luca Franceschini, Manuela Rizzo, Ambra Di Veroli, Luca Maurillo, Giulia Falconi, Emiliano Fabiani, Maria Cantonetti, Ida Provenzano, Daniela Nasso, Francesco Lo-Coco, Maria Luigia Randi, Maria Teresa Voso
Journal: Blood (2018)
Nucleotide-binding oligomerization domain 1 (NOD1) modulates liver ischemia reperfusion through the expression adhesion molecules
Authors: Guillaume Lassailly, Mohamed Bou Saleh, Natascha Leleu-Chavain, Massih Ningarhari, Emilie Gantier, Rodolphe Carpentier, Florent Artru, Viviane Gnemmi, Benjamin Bertin, Patrice Maboudou, Didier Betbeder, Céline Gheeraert, François Maggiotto, Sébastien Dharancy, Philippe Mathurin, Alexandre Louvet, Laurent Dubuquoy
Journal: Journal of Hepatology (2019)
Abstract B02: Distinct CD8+ T-cell recognition profiles driven by conformational plasticity of recurrent neuroblastoma neoepitopes
Authors: Sofie R. Salama, Jugmohit S. Toor, Arjun A. Rao, Andrew C. McShan, Mark Yarmarkovich, Sarvind Tripathi, Santrupti Nerli, Ada A. Madejska, Son Nguyen, Karissa Yamaguchi, John M. Maris, David Haussler, Nikolaos G. Sgourakis
Journal: Cancer Research (2018)

Abstract The identification of tumor neoantigens driving T-cell responses for immunotherapy poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction Of T Cell Epitopes for Cancer Therapy (ProTECT), using sequencing data from neuroblastoma patients to identify a recurrent Anaplastic Lymphoma Kinase mutation (ALK R1275Q) that leads to two high-affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the x-ray structures of nonamer and decamer peptides bound to HLA-B*15:01 reveals that the neoepitopes adopt distinct conformations that confer measurable differences in stability in vitro, while the self-antigen is excluded from binding due to steric hindrance. MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes elicit distinct CD8+ T-cell recognition profiles. To expand the range of patients who could mount a T-cell response to our ALK neoepitopes, we additionally characterize HLA binding repertoire using Rosetta comparative modeling simulations. Subsequent determination of the x-ray structure of decamer-bound HLA-A*01:01 further validates the Rosetta predictions. This work provides a novel approach towards robust, high-throughput identification and detailed characterization of highly stable neoantigen/HLA targets with desired T-cell recognition features for cancer immunotherapy. Citation Format: Sofie R. Salama, Jugmohit S. Toor, Arjun A. Rao, Andrew C. McShan, Mark Yarmarkovich, Sarvind Tripathi, Santrupti Nerli, Ada A. Madejska, Son Nguyen, Karissa Yamaguchi, John M. Maris, David Haussler, Nikolaos G. Sgourakis. Distinct CD8+ T-cell recognition profiles driven by conformational plasticity of recurrent neuroblastoma neoepitopes [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B02.
Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning
Authors: Gergely Farkas Turi, Wen-Ke Li, Spyridon Chavlis, Ioanna Pandi, Justin O’Hare, James Benjamin Priestley, Andres Daniel Grosmark, Zhenrui Liao, Max Ladow, Jeff Fang Zhang, Boris Valery Zemelman, Panayiota Poirazi, Attila Losonczy
Journal: Neuron (2019)
Abstract 030: Natural History of Obesity Subphenotypes: Dynamic Changes Over Two Decades and Prognosis in the Framingham Heart Study
Authors: Justin B Echouffo Tcheugui, Meghan I Short, Todd R Sponholtz, Patrick Field, Vanessa Xanthakis, Martin G Larson, Ramachandran S Vasan
Journal: Circulation (2018)

Introduction: The natural history of obesity (body mass index [BMI]≥30 kg/m 2 ) sub-phenotypes is not fully understood. We investigated longitudinal changes in obesity sub-phenotypes, and their associations with health outcomes. Hypothesis: We hypothesized that metabolically heathy obesity (MHO) is associated with elevated risk of cardiovascular disease [CVD], metabolic disease and cancer, compared to healthy non-obesity. Methods: We evaluated 4,291 Framingham Offspring Study participants attending at least two examinations between cycles 2 [1979-1983] through 7 [1998-2001] (26,508 participant-observations). Obesity subphenotypes were defined using metabolic health (&lt;2 of Adult Treatment Panel-III criteria) and BMI (metabolically healthy non-obese [MHNO], MHO, metabolically unhealthy non-obese [MUNO], metabolically unhealthy obese [MUO]). We assessed changes in subphenotypes over time, and their relations to coronary artery calcification (CAC), subclinical CVD (presence of one or more of the following: left ventricular [LV] systolic dysfunction, LV hypertrophy, increased carotid intima-media thickness, reduced ankle-brachial index or microalbuminuria) and incident diabetes, hypertension, chronic kidney disease, CVD and mortality. Results: At baseline, 4% and 31% of participants exhibited the MHO and MUNO subphenotypes, respectively. Between two consecutive exams, &gt;40% of MHO participants became MUO. Transition probabilities were highest for MHO to MUO changes (43-46%). Compared to MHNO, MHO participants had 1.28-fold and 1.9-fold higher odds of subclinical CVD and CAC, respectively; corresponding values for MUNO were 1.95 and 1.92 ( P &lt;0.05). Compared to MHNO, MHO increased the risks of diabetes and hypertension ( Table ); while MUNO increased the risks of diabetes, hypertension, CVD and death. Conclusion: Over two decades, most MHO participants developed metabolic abnormalities, subclinical and clinical disease, suggesting that this subphenotype is a harbinger of future disease risk.
Abstract 17714: Downregulation of Tgf-ß By CRISPR/Cas9 Attenuates High Glucose-induced Myofibroblast Transformation: A Novel Therapeutic Approach for Treating Cardiac Fibrosis
Authors: Yangxin Li, Bei-bei Lan, Lian-bo Shao, Juan-juan Wang, Yu Zhang, Lu-lu Zhang, Peng-li Xiao, Bin Liu, Chun Liang, Xiangbin Pan, Yong-jian Geng, Zhenya Shen, Xi-yong Yu
Journal: Circulation (2016)

Introduction: Cardiac fibrosis is the leading cause of myocardial dysfunction in patients with diabetes. Myofibroblast transformation is a key factor involved in fibrosis, which is induced by activ...
Circulating tumor DNA testing and research in patients with gastrointestinal malignancies.
Authors: Faisal Shahjehan, Saivaishnavi Kamatham, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2019)

525 Background: The hallmark of circulating tumor DNA (ctDNA) is its rapid turnaround and non-invasive nature. According to American Society of Clinical Oncology (ASCO) and College of American Pathologists joint ctDNA review published in March 2018, there is no sufficient evidence to support the use of ctDNA in practice for GI cancers. However, there were numerous studies presented at ASCO Annual Meeting supporting its value. We aimed to summarizing on its role in the management of gastrointestinal cancers based on the studies presented recently. Methods: We limited our search to keywords ‘ctDNA’, ‘circulating tumor DNA’, ‘cell-free DNA (cfDNA)’ and/or ‘liquid biopsy’, at the 2018 ASCO Annual Meeting library abstracts and presentations. Results: There were 35 studies that revolved around ctDNA as a diagnostic tool, prognostic marker and a measure of tumor heterogeneity in gastrointestinal cancers. Depending on the assay used, the results of several studies showed that ctDNA was able to identify relevant mutations including RAS, HER2/Neu, BRAF, MET, BRCA2, APC, TP53, ROS1, PTEN and NF1. The prognosis in terms of tumor mutation burden, objective response rate, metastasis and survival was also estimated based on ctDNA. The findings showed that higher baseline ctDNA levels and/or increased number of mutations detected in ctDNA were associated with poor survival and multi-site metastasis. Right-sided colon cancer was associated with higher number of mutations in ctDNA than left-sided colon and rectal cancers. Similarly, tubular adenocarcinoma subtype of gastric cancer was more likely to have higher ctDNA levels than signet-ring cell subtype. The response to therapy and the residual metastatic disease which was otherwise not detected on imaging could be detected by ctDNA as well. Conclusions: The research at ASCO 2018 report an increasingly promising role of ctDNA in many forms in patients with gastrointestinal malignancies. Experts at the meeting argued that this may well indeed be ready for prime time for certain GI malignancies including colorectal cancers. Prospective studies and studies showing its feasibility into practice can potentially help revise the current guidelines.
Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study
Authors: Ajinkya Pawar, Rishi J Desai, Daniel H Solomon, Adrian J Santiago Ortiz, Sara Gale, Min Bao, Khaled Sarsour, Sebastian Schneeweiss, Seoyoung C Kim
Journal: Annals of the Rheumatic Diseases (2019)

Objective To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept. Methods Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for &gt;70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis. Results The primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users. Conclusions This large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.
Considering the impact of the flexible polypectomy snare
Authors: Douglas Rex, Heiko Pohl
Journal: Endoscopy (2019)

This year Endoscopy celebrates its 50th birthday by highlighting some of the landmark papers in the history of the journal. In this regard, the 1971 report by Professor P. Deyhle et al. from Erlangen University is certainly an example of a transformative contribution [1]. The authors reported the development of a flexible wire loop diathermic resection snare, which we now refer to in everyday practice as the polypectomy snare. The original oval wire loop snare depicted in the Deyhle paper and shown resecting pedunculated and sessile lesions in [Fig. 1] is immediately recognizable to modern colonoscopists. Though variations in loop shape ([Fig. 1]) and wire construction have developed over time, the persistence of this device in much the same form as it appeared five decades ago is truly remarkable. Using the diathermic snare, Deyhle et al. resected six polyps up to 1.5 cm in size from the colon above the rectum. Whereas polyp resection was previously performed in the rectum using rigid proctoscopes and resection tools, polyp resection in the colon through colonoscopes and using flexible snares was a new paradigm. The trepidation and uncertainty they must have experienced in performing an operation previously possible only by open surgical resection, is suggested by their comment: “Until we have more experience, we consider a period of hospitalization of 5 days after the operation to be necessary.” Contemporaneously, Hiromi Shinya in the USA, in collaboration with Hiroshi Ichikawa and William Wolff, also developed a diathermic snare and applied it above the rectum [2].
Dasatinib Significantly Enhances the Level of Th1 Cells While Decreases the Level of Treg Cells in Chronic Myeloid Leukemia Patients, and Th1 Can be a Potential Marker for Evaluating the Therapeutic Efficacy and Prognosis
Authors: Jingying Dai, Xi Yang, Xiaobing Huang, Hong Zheng, Xiaodong Wang
Journal: Blood (2018)