tbuckley/cabot-search huggingface dataset:
Abstract 276: Impact of Skin Color on Accuracy of Capillary Refill Time Measurement by Pulse Oximeter
Authors: Amanda Nickel, Shen Jiang, Natalie Napolitano, Kota Saeki, Hideaki Hirahara, Vinay Nadkarni, Akira Nishisaki
Journal: Circulation (2018)

Capillary refill time(CRT) is a non-invasive method to assess tissue perfusion, routinely performed in pediatric practice. Current methods to measure CRT have limitations in objectivity and reproducibility. The measurement depends on clinician’s assessment. New analytic approach using pulse oximeter waveform has been developed. Hypothesis: CRT measured by pulse oximeter device and clinicians(critical care/anesthesiologist attending physicians) were different across skin color and finger thickness. Method: Children(1-12 yr) with different skin color tones (Fitzpatrick scale 1-2:fair, 3-4:medium, 5-6:dark) were recruited. Subjects were randomized to a pulse oximeter either on index/middle finger, and had a total 10 CRT measurements (5 with device, 5 with clinician’s visual assessment, alternating). Waveform analysis was performed with quick compression and release on the pulse oximetry device by clinician. The difference between device and clinician measured CRT was calculated. ANOVA for difference in CRT across 3 skin color categories and across 4 finger thickness. Result: 64 subjects(skin color fair 33, medium 16, dark 15) were recruited (median age 72 m, IQR 42-123m). Out of 640 CRT measurements, 300 pairs had measurable CRTs in both device and clinician. Based on clinician’s measurement, 114 CRTs were &gt;2s and 26 CRTs &gt; 4s. The overall CRT difference was mean 0.97±1.32s. The CRT difference by skin color was fair 0.86±1.35s, medium 0.90±1.31s, dark 1.26±1.22s, p=0.095. Pearson correlation coefficient was all 0.49 (fair 0.31, medium 0.67, and dark 0.41, all p&lt;0.001). There was no significant difference in CRT difference among 4 finger thickness categories(thin to thick); 1.21±1.48s, 0.94±1.48s, 1.12±1.20s, 0.75±1.20s, p=0.108. Conclusion: The difference between device and clinician measured CRT did not vary across the different patient skin color or finger thickness. Device measured CRT may be a helpful indicator for peripheral perfusion.
Abstract 172: Ultra-Fast Cooling Through Total Liquid Ventilation is Safe and Feasible in Non-Human Primates
Authors: Matthias Kohlhauer, Emilie Boissady, Fanny Lidouren, Estelle Faucher, Mathieu Nadeau, Bijan Ghaleh, Philippe Micheau, Renaud Tissier
Journal: Circulation (2019)

Introduction: Total liquid ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) provides ultra-rapid and protective cooling in animal models of cardiac arrest. However, the ideal ventilatory parameters still need to be determined for a perfectly safe translation of the procedure in humans, especially regarding expiratory residual volume (RV) and tidal volume of PFC (TV) during TLV. Hypothesis: We hypothetised that TLV with low RV and TV of PFC is safe and efficient for ultra-fast cooling induction in non-human primates. Method: We enrolled two 13-years monkeys ( Macaca Fascicularis ) weighting 10.6 and 11.7 kg, respectively. Lung functional residual capacity (FRC) was measured by CT-scan and 3D-reconstruction of the lung. Two weeks later, animals were anesthetised and submitted to 20 min of TLV with end-expiratory volume of ≈50% of the FRC and TV = 8 ml/kg. The respiratory rate was set to 8/min and the target temperature was 33°C. After the TLV procedure, animals were weaned by prolonged exhalation followed by 6 hours under conventional mechanical ventilation (PEEP = 5 mmHg) before awakening. Three weeks later, they were ansthestized again for blood gases measurement and CT-scan examination for evaluation of the lung parenchyma integrity. Result: The initial CT-scan revealed a FRC of 26 and 32 ml/kg in the two animals, respectively. RV was then set at 15 ml/kg for TLV in both animals. During TLV, gas exchanges were normal (arterial partial pressure of CO 2 was 34 and 43 mmHg, respectively). Pulse oxymetry also remained above 97% throughout TLV. The target temperature of 33°C was achieved in the entire body within 15 min for both animals. Additionally, lung static compliance was not altered during or after TLV. After animal weaning, no any sign of respiratory discomfort was evidenced despite careful clinical monitoring. After three weeks, CT-scan examination revealed no structural abnormality of the lung parenchym and arterial partial pressure of CO 2 was normal (35 and 46 mmHg). Based on their excellent health status, animals were transferred to a rehabilitation center. Conclusion: Total liquid ventilation below FRC is feasible and safe, without any impairement of the cooling performance in a clinically relevant non-human primate model.
Publisher Correction: Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes
Authors: Bjoern Chapuy, Chip Stewart, Andrew J. Dunford, Jaegil Kim, Atanas Kamburov, Robert A. Redd, Mike S. Lawrence, Margaretha G. M. Roemer, Amy J. Li, Marita Ziepert, Annette M. Staiger, Jeremiah A. Wala, Matthew D. Ducar, Ignaty Leshchiner, Ester Rheinbay, Amaro Taylor-Weiner, Caroline A. Coughlin, Julian M. Hess, Chandra S. Pedamallu, Dimitri Livitz, Daniel Rosebrock, Mara Rosenberg, Adam A. Tracy, Heike Horn, Paul van Hummelen, Andrew L. Feldman, Brian K. Link, Anne J. Novak, James R. Cerhan, Thomas M. Habermann, Reiner Siebert, Andreas Rosenwald, Aaron R. Thorner, Matthew L. Meyerson, Todd R. Golub, Rameen Beroukhim, Gerald G. Wulf, German Ott, Scott J. Rodig, Stefano Monti, Donna S. Neuberg, Markus Loeffler, Michael Pfreundschuh, Lorenz Trümper, Gad Getz, Margaret A. Shipp
Journal: Nature Medicine (2018)
Timp1 gene demethylation contributes to the anoikis resistance phenotype along melanocyte malignant transformation
Authors: Tatiana Ricca, Gangning Liang, Ana Suenaga, Mariangela Correa, Sang Han, Peter Jones, Miriam Jasiulionis
Journal: Cancer Research (2007)

2877  Although anoikis resistance has been considered a hallmark of the malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. To study this correlation, we developed an experimental model of murine melanocyte malignant transformation, where different melanoma cell lines (4C3, 4C11, Tm1, Tm5) were established after submitting a non-tumorigenic melanocyte lineage (melan-a) to sequential substrate anchorage impediment cycles. Melan-a sublines, submitted to 2, 3 and 4 deadhesion cycles (2C, 3C and 4C), were also established, showing progressive anoikis-resistance, and representing distinct phases of tumor progression. Previous gene expression analysis comparing adherent melan-a, melan-a maintained in suspension for 24h, adherent Tm1 and Tm5 cells, showed an up-regulation of Timp1 in melanoma cell lines. Although initially described as a MMP inhibitor, this protein has been recently associated with anoikis resistance in human breast tumor cells. Timp1 protein increases along melanocyte tranformation and its possible association with anoikis resistance prompted us to investigate whether Timp1 expression is regulated by DNA methylation and whether it is associated with the acquisition of the anoikis-resistant phenotype. While melan-a cells express low levels of Timp1, all cell lines derived from melan-a express high levels of this protein. After 5AZAdC treatment, increased levels of Timp1 mRNA were observed in melan-a cells, suggesting that in these cells Timp1 expression is regulated by promoter hypermethylation. Ms-SNuPE analysis has shown an increased demethylation in Timp1 promoter and first exon along melan-a carcinogenesis. Overexpression of Timp1 in melan-a cells resulted in increased survival in anchorage-independent conditions, but Timp1 overexpression by itself was unable to transform non-tumorigenic melanocytes into tumor-forming cell lines. In addition, latency time for tumor appearance was reduced in Timp1-transfected Tm5 melanoma cells, indicating that this molecule may be associated with tumor aggressiveness. In conclusion, our results show a progressive increment in Timp1 expression along the malignant transformation process, resulting from progressive promoter demethylation, which is causally associated with an increase in anoikis-resistance but not with the acquisition, by itself, of a fully transformed malignant phenotype.
Colon Adenocarcinoma Associated With Clostridium Septicum Endophthalmitis Detected on 18F-FDG PET/CT
Authors: Nicolas Plouznikoff, Carlos Artigas, Erwin Woff, Diana Ene, Patrick Flamen
Journal: Clinical Nuclear Medicine (2020)

Abstract Endogenous Clostridium septicum endophthalmitis is a rare and fulminant ocular infection, usually encountered in immunocompromised or diabetic patients. It is also highly associated with both gastrointestinal and hematologic malignancies. We describe herein the detection of an adenocarcinoma of the cecum on PET/CT with 18 F-FDG in a patient with an active endogenous C. septicum endophthalmitis of the right eye. FDG PET/CT should be considered for all patients with endogenous endophthalmitis to exclude an occult malignancy, especially colorectal cancer.
Hyperestrogenism on 18F-FDG PET/CT in a Patient With Estrogen-Producing Ovarian Clear Cell Carcinoma
Authors: Sho Koyasu, Tomoaki Otani, Sachiko Minamiguchi, Yuji Nakamoto, Kaori Togashi
Journal: Clinical Nuclear Medicine (2020)

Abstract A 78-year-old woman was referred to the gynecologic outpatient department because she was suspected of having ovarian cancer based on an imaging study performed during a general medical examination. Further examination using 18 F-FDG PET/CT revealed a bulky mass lesion with low FDG avidity, as well as surprisingly strong bilateral breast radiotracer uptake despite the patient's age. Thus, an estrogen-producing tumor was suspected. Bilateral salpingo-oophorectomy was performed, and surgical pathology diagnosed the tumor as clear cell carcinoma of the ovary.
Frequent occurrence of CD19-negative relapse after CD19 CAR T and consolidation therapy in 14 TP53-mutated r/r B-ALL children
Authors: Jing Pan, Yue Tan, Biping Deng, Chunrong Tong, Lin Hua, Zhuojun Ling, Weiliang Song, Jinlong Xu, Jiajia Duan, Zelin Wang, Huilin Guo, Xinjian Yu, Alex H. Chang, Qinlong Zheng, Xiaoming Feng
Journal: Leukemia (2020)
Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome
Authors: Takako Yokomizo-Nakano, Sho Kubota, Jie Bai, Ai Hamashima, Mariko Morii, Yuqi Sun, Seiichiro Katagiri, Mihoko Iimori, Akinori Kanai, Daiki Tanaka, Motohiko Oshima, Yuka Harada, Kazuma Ohyashiki, Atsushi Iwama, Hironori Harada, Motomi Osato, Goro Sashida
Journal: Cancer Research (2020)

RUNX3, a RUNX family transcription factor, regulates normal hematopoiesis and functions as a tumor suppressor in various tumors in humans and mice. However, emerging studies have documented increased expression of RUNX3 in hematopoietic stem/progenitor cells (HSPC) of a subset of patients with myelodysplastic syndrome (MDS) showing a worse outcome, suggesting an oncogenic function for RUNX3 in the pathogenesis of hematologic malignancies. To elucidate the oncogenic function of RUNX3 in the pathogenesis of MDS in vivo, we generated a RUNX3-expressing, Tet2-deficient mouse model with the pancytopenia and dysplastic blood cells characteristic of MDS in patients. RUNX3-expressing cells markedly suppressed the expression levels of Runx1, a critical regulator of hemaotpoiesis in normal and malignant cells, as well as its target genes, which included crucial tumor suppressors such as Cebpa and Csf1r. RUNX3 bound these genes and remodeled their Runx1-binding regions in Tet2-deficient cells. Overexpression of RUNX3 inhibited the transcriptional function of Runx1 and compromised hematopoiesis to facilitate the development of MDS in the absence of Tet2, indicating that RUNX3 is an oncogene. Furthermore, overexpression of RUNX3 activated the transcription of Myc target genes and rendered cells sensitive to inhibition of Myc-Max heterodimerization. Collectively, these results reveal the mechanism by which RUNX3 overexpression exerts oncogenic effects on the cellular function of and transcriptional program in Tet2-deficient stem cells to drive the transformation of MDS. SIGNIFICANCE: This study defines the oncogenic effects of transcription factor RUNX3 in driving the transformation of myelodysplastic syndrome, highlighting RUNX3 as a potential target for therapeutic intervention.
Microtubule Engagement with Taxane Is Altered in Taxane-Resistant Gastric Cancer
Authors: Giuseppe Galletti, Chao Zhang, Ada Gjyrezi, Kyle Cleveland, Jiaren Zhang, Sarah Powell, Prashant V. Thakkar, Doron Betel, Manish A. Shah, Paraskevi Giannakakou
Journal: Clinical Cancer Research (2020)

Although taxane-based therapy is standard treatment for advanced gastric cancer, a majority of patients exhibit intrinsic resistance to taxanes. Here, we aim to identify the molecular basis of taxane resistance in gastric cancer.We performed a post hoc analysis of the TAX-325 clinical trial and molecular interrogation of gastric cancer cell lines to assess the benefit of docetaxel in diffuse (DIF-GC) versus intestinal (INT-GC) gastric cancer. We assessed drug-induced microtubule stabilization in gastric cancer cells and in biopsies of patients with gastric cancer treated with taxanes. We performed transcriptome analysis in taxane-treated gastric cancer cells and patients to identify molecular drivers of taxane resistance.Patients with DIF-GC did not derive a clinical benefit from taxane treatment suggesting intrinsic taxane resistance. DIF-GC cell lines displayed intrinsic resistance specific to taxanes because of impaired drug-induced microtubule stabilization, in the absence of tubulin mutations or decreased drug accumulation. Using taxane-treated gastric cancer patient biopsies, we demonstrated that absence of drug-target engagement was correlated with clinical taxane resistance. Taxane-sensitive cell lines displayed faster microtubule dynamics at baseline, implicating proteins that regulate cytoskeletal dynamics in intrinsic taxane resistance. Differential gene expression analysis of untreated and docetaxel-treated gastric cancer lines and patient samples identified kinesins to be associated with taxane sensitivity in vitro and in patient samples.Our data reveal that taxane resistance is more prevalent in patients with DIF-GC, support assessment of drug-target engagement as an early read-out of taxane clinical efficacy, and encourage the investigation of kinesins and other microtubule-associated proteins as potentially targetable mediators of taxane resistance in gastric cancer.
Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis
Authors: Federica Jiritano, Giuseppe Filiberto Serraino, Hugo ten Cate, Dario Fina, Matteo Matteucci, Pasquale Mastroroberto, Roberto Lorusso
Journal: Intensive Care Medicine (2020)

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.
Primary Retinal Detachment Outcomes Study Report Number 2
Authors: Edwin H. Ryan, Claire M. Ryan, Nora J. Forbes, Yoshihiro Yonekawa, Sushant Wagley, Robert A. Mittra, D. Wilkin Parke, Daniel P. Joseph, Geoffrey G. Emerson, Gaurav K. Shah, Kevin J. Blinder, Antonio Capone, George A. Williams, Dean Eliott, Omesh P. Gupta, Jason Hsu, Carl D. Regillo
Journal: Ophthalmology (2020)
Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments
Authors: Chao Gao, Jun Liu, Yuyan Tan, Shengdi Chen
Journal: Translational Neurodegeneration (2020)

Abstract Background Freezing of gait (FOG) is a common, disabling symptom of Parkinson’s disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed. Main body In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising. Conclusion FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.
Abstract 11533: Dose-dependent Inhibitory Effect of Rosuvastatin in Japanese Patients With Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases - Invitation Trial -
Authors: Koichiro Fujisue, Takuhiro Shirakawa, Shinichi Nakamura, Nobuyasu Yamamoto, Shuichi Oshima, Toshiyuki Matsumura, Ryusuke Tsunoda, Nobutaka Hirai, Shinji Tayama, Natsuki Nakamura, Toyoki Hirose, Kazuteru Fujimoto, Hideki Shimomura, Yasuhiro Izumiya, Koichi Kaikita, Hisao Ogawa, Kenichi Tsujita
Journal: Circulation (2019)

Backgrounds: Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a...
移植後ドナー白血球輸血(DLT)による移植片対白血病/リンパ腫(GVL)効果と慢性移植片対宿主病(GVHD)活性化との関係:急性白血病または悪性リンパ腫15症例の報告
Authors: Takahashi S, Shirafuji N, Nagayama H, Shindo E, Tanaka H, Wakumoto Y, Sato K, Okamoto S, Tojo A, Tani K, Wakabayashi M, Sato N, Maekawa T, Nakahata T, Asano S
Journal: Blood (1996)
Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials
Authors: Stéphane Gaudry, David Hajage, Nicolas Benichou, Khalil Chaïbi, Saber Barbar, Alexander Zarbock, Nuttha Lumlertgul, Ron Wald, Sean M Bagshaw, Nattachai Srisawat, Alain Combes, Guillaume Geri, Tukaram Jamale, Agnès Dechartres, Jean-Pierre Quenot, Didier Dreyfuss
Journal: The Lancet (2020)
Human influenza A virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death
Authors: David Filgueiras-Rama, Jasmina Vasilijevic, Jose Jalife, Sami F Noujaim, Jose M Alfonso, Jose A Nicolas-Avila, Celia Gutierrez, Noelia Zamarreño, Andres Hidalgo, Alejandro Bernabé, Christopher Pablo Cop, Daniela Ponce-Balbuena, Guadalupe Guerrero-Serna, Daniel Calle, Manuel Desco, Jesus Ruiz-Cabello, Amelia Nieto, Ana Falcon
Journal: Cardiovascular Research (2020)

Abstract Aims Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations. Methods and results We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase. Conclusion Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death.