tbuckley/cabot-search huggingface dataset:
Blood and skin-derived Sezary cells: differences in proliferation-index, activation of PI3K/AKT/mTORC1 pathway and its prognostic relevance
Authors: Cristina Cristofoletti, Antonella Bresin, Mario Picozza, Maria Cristina Picchio, Francesca Monzo, Mauro Helmer Citterich, Francesca Passarelli, Alessandra Frezzolini, Enrico Scala, Alessandro Monopoli, Maria Cantonetti, Roberto Benucci, Stefania D’Atri, Elisabetta Caprini, Giandomenico Russo, Maria Grazia Narducci
Journal: Leukemia (2018)

Sézary syndrome (SS) is a rare and aggressive variant of Cutaneous T-Cell Lymphoma characterized by neoplastic distribution mainly involving blood, skin, and lymph-node. Although a role of the skin microenvironment in SS pathogenesis has long been hypothesized, its function in vivo is poorly characterized. To deepen this aspect, here we compared skin to blood-derived SS cells concurrently obtained from SS patients highlighting a greater proliferation-index and a PI3K/AKT/mTORC1 pathway activation level, particularly of mTOR protein, in skin-derived-SS cells. We proved that SDF-1 and CCL21 chemokines, both overexpressed in SS tissues, induce mTORC1 signaling activation, cell proliferation and Ki67 up-regulation in a SS-derived cell line and primary-SS cells. In a cohort of 43 SS cases, we observed recurrent copy number variations (CNV) of members belonging to this cascade, namely: loss of LKB1 (48%), PTEN (39%) and PDCD4 (35%) and gains of P70S6K (30%). These alterations represent druggable targets unraveling new therapeutic treatments as metformin here evaluated in vitro. Moreover, CNV of PTEN, PDCD4, and P70S6K, evaluated individually or in combination, are associated with reduced survival of SS patients. These data shed light on effects in vivo of skin-SS cells interaction underlying the prognostic and therapeutic relevance of mTORC1 pathway in SS.
5 Year Health Care Burden after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Impact of Graft Source
Authors: Jesus Garcia Garcia, Sonya Grillo, Qing Cao, Claudio G Brunstein, Mukta Arora, Margaret L. MacMillan, John E. Wagner, Daniel J. Weisdorf, Shernan G. Holtan
Journal: Blood (2018)
Enhancer Architecture and Essential Core Regulatory Circuitry of Chronic Lymphocytic Leukemia
Authors: Christopher J. Ott, Alexander J. Federation, Logan S. Schwartz, Siddha Kasar, Josephine L. Klitgaard, Romina Lenci, Qiyuan Li, Matthew Lawlor, Stacey M. Fernandes, Amanda Souza, Donald Polaski, Deepti Gadi, Matthew L. Freedman, Jennifer R. Brown, James E. Bradner
Journal: Cancer Cell (2018)
Adenocarcinoma of the Vagina
Authors: Arthur L. Herbst, Howard Ulfelder, David C. Poskanzer
Journal: New England Journal of Medicine (1971)

Adenocarcinoma of the vagina in young women had been recorded rarely before the report of several cases treated at the Vincent Memorial Hospital between 1966 and 1969. The unusual occurrence of this tumor in eight patients born in New England hospitals between 1946 and 1951 led us to conduct a retrospective investigation in search of factors that might be associated with tumor appearance. Four matched controls were established for each patient; data were obtained by personal interview. Results show maternal bleeding during the current pregnancy and previous pregnancy loss were more common in the study group. Most significantly, seven of the eight mothers of patients with carcinoma had been treated with diethylstilbestrol started during the first trimester. None in the control group were so treated (p less than 0.00001). Maternal ingestion of stilbestrol during early pregnancy appears to have enhanced the risk of vaginal adenocarcinoma developing years later in the offspring exposed.
Association of impairments in activities of daily living (ADLs) with symptom burden, health care utilization, and survival among hospitalized patients with advanced cancer.
Authors: Daniel E Lage, Areej El-Jawahri, Charn-Xin Fuh, Richard Newcomb, Vicki Jackson, Joseph Greer, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2018)

203 Background: Hospitalized patients with cancer often have impaired ADLs related to age, comorbidities, and both cancer and treatment-related morbidity. However, the relationship between ADL impairment and patients’ symptom burden and clinical outcomes has not been well described. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations at an academic medical center. Upon admission, nurses assessed patients’ ADLs (mobility, feeding, bathing, dressing, and grooming). We used the Edmonton Symptom Assessment Scale (ESAS) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, comparing symptom burden between patients with and without ADL impairment. We used regression models adjusted for age, sex, education, Charlson comorbidity index, months since advanced cancer diagnosis, and cancer type to assess the relationship between any ADL impairment and hospital length of stay, the composite outcome of death or readmission within 90 days of discharge, and survival. Results: Among 932 patients, 40.2% had at least one ADL impairment. Patients with ADL impairment were older (67.2 vs. 60.8 years, p&lt;0.001), had higher Charlson comorbidity index (1.1 vs. 0.7, p&lt;0.001), and higher physical symptom burden (ESAS Physical 35.2 vs. 30.9, p&lt;0.001). Those with ADL impairment were more likely to have moderate to severe constipation (46.7% vs. 36.0%, p&lt;0.01), pain (74.9% vs. 63.1%, p&lt;0.01), drowsiness (76.6% vs. 68.3%, p&lt;0.01), as well as symptoms of depression (38.3% vs. 23.6%, p&lt;0.01) and anxiety (35.9% vs. 22.4%, p&lt;0.01). In adjusted models, ADL impairment was associated with longer hospital length of stay (B=1.30, p&lt;0.01), higher odds of death or readmission within 90 days (odds ratio=2.26, p&lt;0.01), and worse survival (hazard ratio=1.73, p&lt;0.01). Conclusions: Hospitalized patients with advanced cancer who have ADL impairment experience a significantly higher symptom burden and worse health outcomes compared to those without ADL impairment. These findings highlight the need to assess and address ADL impairment among this population to enhance their quality of life and care.
Abstract 10819: Prognostic Value of Coronary Artery Calcium Score in Acute Chest Pain Patients Without Known Coronary Artery Disease in Emergency Department: Systematic Review and Meta-analysis
Authors: Kongkiat Chaikriangkrai, Patompong Ungprasert, Hye Yeon Jhun, Faisal Nabi, John Mahmarian, Su Min Chang
Journal: Circulation (2015)

Backgrounds: Role of coronary artery calcium score (CACS) in acute chest pain patients is currently not well defined. The objective of this study was to investigate the prognostic value of CACS obtained by noncontrast electrocardiogram-gated CT in acute chest pain patients suspected for cardiac origin in emergency department. Methods: We search Pubmed, Embase, Cochrane databases for longitudinal studies of CACS in acute chest pain patients without known coronary artery disease (CAD) in emergency department which reported major adverse cardiovascular events (MACE), consisting of death, nonfatal myocardial infarction (NFMI), revascularization or stroke. Pooled annualized event rate, risk ratios and 95% confidence intervals (CI) were analyzed. A random-effect, generic inverse variance model was used. Result: Eight studies evaluated 3556 patients (mean age = 51 years, 47% men) with the pooled prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking of 42%, 16%, 33% and 33% respectively. During a median follow-up of 5 months (range 1-60 months, 37234 patient-months), the overall pooled MACE rate was 7.6%/y. The pooled event rate of MACE for CACS=0 versus CACS&gt;0 was 0.8%/y (13 events in 18874 patient-months) versus 14.6%/y (224 events in 18360 patient-months). The pooled risk ratio with CACS=0 was 0.04 (95% CI: 0.02-0.07, p&lt;0.001) for MACE compared to CACS&gt;0. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of CACS for MACE was 94.5%, 64.1%, 15.8%, 99.4%, 2.63 and 0.09 respectively. The heterogeneity among studies was low with an I 2 of 13%. Conclusion: In acute-chest-pain patients without known CAD presenting to emergency department, MACE was rare in those with CACS=0. Zero CACS by noncontrast electrocardiogram-gated CT in this population has high negative predictive value (&gt;99%) for subsequent cardiac events.
2018 Update on Medical Overuse
Authors: Daniel J. Morgan, Sanket S. Dhruva, Eric R. Coon, Scott M. Wright, Deborah Korenstein
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Overuse of medical care is a well-recognized problem in health care, associated with patient harm and costs. We sought to identify and highlight original research articles published in 2017 that are most relevant to understanding medical overuse. <h3>Observations</h3> A structured review of English-language articles published in 2017 was performed, coupled with examination of tables of contents of high-impact journals to identify articles related to medical overuse in adult care. Manuscripts were appraised for their quality, clinical relevance, and impact. A total of 1446 articles were identified, 910 of which addressed medical overuse. Of these, 111 articles were deemed to be the most relevant based on originality, methodologic quality, and scope. The 10 most influential articles were selected by author consensus. Findings included that unnecessary electrocardiograms are common (performed in 22% of patients at low risk) and can lead to a cascade of services, lipid monitoring rarely affects care, patients who were overdiagnosed with cancer experienced anxiety and criticism about not seeking treatment, calcium and vitamin D supplementation does not reduce hip fracture (relative risk, 1.09; 95% CI, 0.85-1.39), and pregabalin does not improve symptoms of sciatica but frequently has adverse effects (40% of patients experienced dizziness). Antipsychotic medications increased the severity of delirium in patients receiving hospice care and were associated with an increased risk of death (hazard ratio, 1.7;<i>P</i> = .003), and robotic-assisted radical nephrectomy was without benefits by being slower and more costly than laparoscopic surgery. High-sensitivity troponin testing often yielded false-positive results, as 16% of patients with positive troponin results in a US hospital had a myocardial infarction. One-third of patients who received a diagnosis of asthma had no evidence of asthma. Restructuring the electronic health record was able to reduce unnecessary testing (from 31.3 to 13.9 low-value tests performed per 100 patient visits). <h3>Conclusions and Relevance</h3> Many current practices were found to represent overuse, with no benefit and potential harms. Other services were used inappropriately. Reviewing these findings and extrapolating to their patients will enable health care professionals to improve the care they provide.
Abstract 20179: Early Recovery From Hypotension and Lactate Acidosis for Good Neurological Outcome in Out-of-Hospital Cardiac Arrest Patients
Authors: Su Jin Kim, Kap Su Han, Jong Su Park, sung woo Lee
Journal: Circulation (2017)

Objective: To find the relationship between the levels of blood pressure or serum lactate and the good neurologic outcome and to determine whether the early recovery from hypotension and lactic aci...
Loss-of-Function Mutations in Dnmt3a and Tet2 Lead to Accelerated Atherosclerosis and Convergent Macrophage Phenotypes in Mice
Authors: Philipp J. Rauch, Alexander J. Silver, Jk Gopakumar, Marie McConkey, Eti Sinha, Maia Fefer, Eugenia Shvartz, Galina Sukhova, Peter Libby, Benjamin L. Ebert, Siddhartha Jaiswal
Journal: Blood (2018)
Diagnostic performance of plasma cytokine biosignature combination and MCP-1 as individual biomarkers for differentiating stages Mycobacterium tuberculosis infection
Authors: Jie Luo, Mingxu Zhang, Baosong Yan, Fake Li, Shaonian Guan, Kai Chang, Wenbin Jiang, Huan Xu, Tao Yuan, Ming Chen, Shaoli Deng
Journal: Journal of Infection (2018)
Nurses and health care assistants: Evaluation of attitude towards the care of patients who are terminally ill with cancer.
Authors: Diego Lopane, Carlotta Pavesi, Concetta Arcanà, Gaia Morazzoni, Diego Lopane, Stefano Ferrari, Santina Giuffrè, Chiara Poggio, Daria Banfi, Giulia Lamiani, Annalisa Saetta, Lorenza Rimassa, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

158 Background: Terminally ill cancer patients (pts) are often hospitalized in the last 3 months of life, and a large number of them die in hospital. They require specific care provided by a team of health professionals with expertise in palliative (PC) and end-of-life care (EoLC). The aim of this analysis is to investigate the attitudes of nurses (Ns) and health care assistants (HCAs) towards terminally ill patients in a Cancer Center (CC). Methods: From July to November 2017 we applied the Frommelt Attitudes Toward Care of the Dying FORM-B Scale (FATCOD) to Ns and HCAs working in a CC, situated in a metropolitan area in Italy. FATCOD is a validated tool in its Italian version, composed of 30 questions investigating 6 specific areas: Fear (Fe), Communication (Co), Relationship (Rs), Care of the family (CoF), Family as Caring (FaC), Active Care (Ac). Each question has 5 answer options: strongly disagree, disagree, don’t know, agree, strongly agree, with scores from 1, negative, to 5, positive attitude. The total score ranges from 30 to 150. Results: We administered 116 questionnaires, 102 (87.9%) were completed. 81 Ns were involved (79.4%, 31/50 males/females) and 21 HCAs (20.6%, 4/17 males/females). The median age of Ns was 39 years (range 20-50) and 43 for the HCAs (range 30-50). The median duration of employment was 10 years for both groups (range 0-20). The median score achieved by both groups was 110.3 (range 78-140). Ns obtained a score of 112.1 (range 98.7-125.5), HCAs of 103.4 (range 89.4-117.7). Our analysis shows a positive attitude in both groups across 3 areas ( FaC, CoF, AC) and a negative one in others (Fe, Co, Rs), with a statistically significant concordance between the 2 groups (p=0.0037). Conclusions: Data shows NS and HCAs negative attitude in 3 important areas, with scores below the average results reported in literature. Based on our results, we proposed some intervention strategies. We organized periodic meetings with our psychologists. Our Institution introduced the PERCS ( Program to Enhance Relational and Communication Skills) and specific programs in medical and nursing schools of our university, favoring the earliest approach to PC and EoLC. We also provided seminars in PC to Ns and HCAs working in the CC.
Validity of the EQ-5D in pemphigus vulgaris and foliaceus patients
Authors: B. Tamási, V. Brodszky, M. Péntek, L. Gulácsi, K. Hajdu, M. Sárdy, A. Szegedi, Z. Bata-Csörgő, Á. Kinyó, F. Rencz
Journal: British Journal of Dermatology (2018)
Long-Term Survivorship Care After Cancer Treatment - Summary of a 2017 National Cancer Policy Forum Workshop
Authors: Ronald M Kline, Neeraj K Arora, Cathy J Bradley, Eden R Brauer, Darci L Graves, Natasha Buchanan Lunsford, Mary S McCabe, Shelley Fuld Nasso, Larissa Nekhlyudov, Julia H Rowland, Rebekkah M Schear, Patricia A Ganz
Journal: JNCI Journal of the National Cancer Institute (2018)

The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)'s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer's (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation's Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.
Targeted homing of CCR2-overexpressing mesenchymal stromal cells to ischemic brain enhances post-stroke recovery partially through PRDX4-mediated blood-brain barrier preservation
Authors: Yinong Huang, Jiancheng Wang, Jianye Cai, Yuan Qiu, Haiqing Zheng, Xiaofan Lai, Xin Sui, Yi Wang, Qiying Lu, Yanan Zhang, Meng Yuan, Jin Gong, Wei Cai, Xin Liu, Yilong Shan, Zhezhi Deng, Yue Shi, Yaqing Shu, Lei Zhang, Wei Qiu, Lisheng Peng, Jie Ren, Zhengqi Lu, Andy Peng Xiang
Journal: Theranostics (2018)

Rationale: Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic strategy for the acute ischemic stroke (AIS).However, the poor targeted migration and low engraftment in ischemic lesions restrict their treatment efficacy.The ischemic brain lesions express a specific chemokine profile, while cultured MSCs lack the set of corresponding receptors.Thus, we hypothesize that overexpression of certain chemokine receptor might help in MSCs homing and improve therapeutic efficacy.Methods: Using the middle cerebral artery occlusion (MCAO) model of ischemic stroke, we identified that CCL2 is one of the most highly expressed chemokines in the ipsilateral hemisphere.Then, we genetically transduced the corresponding receptor, CCR2 to the MSCs and quantified the cell retention of MSC CCR2 compared to the MSC dtomato control.Results: MSC CCR2 exhibited significantly enhanced migration to the ischemic lesions and improved the neurological outcomes.Brain edema and blood-brain barrier (BBB) leakage levels were also found to be much lower in the MSC CCR2 -treated rats than the MSC dtomato group.Moreover, this BBB protection led to reduced inflammation infiltration and reactive oxygen species (ROS) generation.Similar results were also confirmed using the in vitro BBB model.Furthermore, genome-wide RNA sequencing (RNA-seq) analysis revealed that peroxiredoxin4 (PRDX4) was highly expressed in MSCs, which mainly contributed to their antioxidant impacts on MCAO rats and oxygen-glucose deprivation (OGD)-treated endothelium.Conclusion: Taken together, this study suggests that overexpression of CCR2 on MSCs enhances their targeted migration to the ischemic hemisphere and improves the therapeutic outcomes, which is attributed to the PRDX4-mediated BBB preservation.
Relapse of porphyria cutanea tarda after treatment
Authors: H. Salameh, H. Sarairah, M. Rizwan, Y.-F. Kuo, K.E. Anderson, A.K. Singal
Journal: British Journal of Dermatology (2018)

Porphyria cutanea tarda (PCT) is a skin disease causing a rash and sunlight sensitivity. Patients affected by this condition can be treated by removing some of their blood, or with a medication that is also used to prevent and treat malaria (antimalarials). In this study, the authors compared the effectiveness of these quite different treatment approaches. They included data on patients, from previous clinical studies, who were treated for PCT and monitored for at least one year after their symptoms had cleared. They aimed to assess PCT disease recurrence (i.e. the symptoms returning) either by skin rash, sunlight sensitivity or an elevation in a certain blood test. Authors included data on patients from 5 clinical studies in which patients received high dose of antimalarial medication, 5 clinical studies in which patients received low dose antimalarial medication and 3 clinical studies in which patients were treated by removing some of their blood. While one third of the patients treated with either high or low dose antimalarial medication experienced disease recurrence, only one fifth of patients treated by removing blood experienced such disease recurrence. Their study showed that if 100 patients were followed for one year, disease recurrence will happen in 8 patients receiving high dose antimalarials, 17 patients receiving low dose antimalarials, and 5 patients undergoing blood removal. The authors concluded that the recurrence is lowest if the PCT is treated by blood removal. However, larger studies are needed to better define recurrence rate of PCT after treatment with one of the two treatments.
Human cardiomyocytes undergo enhanced maturation in embryonic stem cell-derived organoid transplants
Authors: Fahimeh Varzideh, Sara Pahlavan, Hassan Ansari, Majid Halvaei, Sawa Kostin, Mohammad-Sadegh Feiz, Hamid Latifi, Nasser Aghdami, Thomas Braun, Hossein Baharvand
Journal: Biomaterials (2018)
Abstract 13712: Serum HDL Cholesterol Decreases in Microrna-33b Knock-in Mice for an Intron of Sterol Regulatory Element-binding Factor 1 (Srebf1)
Authors: Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Naoya Sowa, Yasuhiro Nakashima, Daihiko Hakuno, Takeshi Kimura, Koh Ono
Journal: Circulation (2015)

Background: MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33 (miR-33a) located within the intron of sterol regulatory element-binding factor (SREBF) 2 controls cholesterol homeostasis. Primates, but not rodents, express a second miR-33 gene (miR-33b) from an intron of SREBF1. To address miR-33b function in vivo, we developed humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron. Methods: The human miR-33b sequence was introduced into intron 16 of mouse Srebf1 because miR-33b is located in intron 16 of human SREBF1 and there are high homologies in exons 16 and 17 between human and mouse. The expression of serum miRNA was normalized with cel-miR-39 as a spike-in control. Results: We successfully established miR-33b knock-in (KI) mice with C57BL/6 background and this miR-33b KI strategy did not alter Srebf1 intron 16 splicing, which was confirmed by RT-PCR and sequencing. An LXR agonist T0901317, which induces Srebf1 expression, enhanced miR-33b expression in primary hepatocytes and the liver of miR-33 KI mice. The protein levels of known miR-33a target genes, such as ABCA1, ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. Peritoneal macrophages from the miR-33b KI mice had a reduced cholesterol efflux capacity via apoA-I and HDL-C. Serum HDL-C levels were reduced by almost 35% in miR-33b KI mice. HPLC elution analysis showed that the decreased HDL-C levels were mainly composed of very large-, large-, medium sized HDL-C, which was compatible with the previous results of miR-33a deficient mice. Next, we measured miR-33b levels in serum of human. The expressions of miR-33b-3p were inversely correlated with serum HDL-C levels (P=0.025, R=0.336). Conclusions: miR-33b KI mice for an intron of Srebf1 showed reduced HDL-C level and serum miR-33b-3p levels were inversely correlated with HDL-C levels in human. These results indicate that miR-33b can be a potential target for raising HDL-C and may account for lower HDL-C levels in humans than those in mice. These mice will aid in elucidating the roles of miR-33s and screening of the drugs that can alter miR-33s levels and activities.