tbuckley/cabot-search huggingface dataset:
Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury
Authors: Sahra Bodo, Cécile Campagne, Tin Htwe Thin, Daniel S. Higginson, H. Alberto Vargas, Guoqiang Hua, John D. Fuller, Ellen Ackerstaff, James Russell, Zhigang Zhang, Stefan Klingler, HyungJoon Cho, Matthew G. Kaag, Yousef Mazaheri, Andreas Rimner, Katia Manova-Todorova, Boris Epel, Joan Zatcky, Cristian R. Cleary, Shyam S. Rao, Yoshiya Yamada, Michael J. Zelefsky, Howard J. Halpern, Jason A. Koutcher, Carlos Cordon-Cardo, Carlo Greco, Adriana Haimovitz-Friedman, Evis Sala, Simon N. Powell, Richard Kolesnick, Zvi Fuks
Journal: Journal of Clinical Investigation (2018)

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.
Dementia: brief cognitive assessments often misclassify condition
Authors: Jacqui Wise
Journal: BMJ (2018)

Dementia is often misclassified when using brief cognitive assessments, which can delay access to treatment and support, say researchers. These tests are widely used in primary care settings to evaluate thinking and memory skills.

The study, published in the journal Neurology ,1 evaluated three tests: the Mini-Mental State Examination, which looks at orientation regarding time and place and the ability to remember words; the Memory Impairment Screen, which focuses on the ability to remember words; and Animal Naming, which involves naming as …
The rate and treatment outcome of thiamine deficiency in cancer patients diagnosed with delirium: A preliminary study.
Authors: Hideki Onishi, Mayumi Ishida, Nozomu Uchida, Izumi Sato, Takao Takahashi
Journal: Journal of Clinical Oncology (2018)

205 Background: Vitamin B1 is essential for life, but cannot be synthesized in vivo and must be ingested from outside the body. Retention in the body is as short as 18 days, so that long-term appetite loss can easily lead to vitamin B1 deficiency, resulting in a condition known as Wernicke's encephalopathy (WE), which is characterized by disturbed consciousness, ataxia, and ocular movement disorders. Early detection and treatment with intravenous vitamin B1 usually results in recovery without sequelae, while a delay in detection can lead to severe brain damage (Korsakoff syndrome). The mortality rate is approximately 20%. Recent studies have shown that cancer patients may also experience thiamine deficiency and WE. WE is often overlooked as the typical symptoms are nonspecific, and some cases do not exhibit the disturbed consciousness characteristic of WE. Clinical awareness can be improved by confirming the actual rate and clarifying the associated symptoms, leading to more accurate WE diagnosis. Methods: We retrospectively examined the medical records for patients admitted to Saitama Medical University International Medical Center between 1 October 2014 and 31 May 2018 with cancer as the main disease who consulted the Psycho-oncology Department and were diagnosed with delirium by a psychiatrist. Patient background, medical treatment, neurological symptoms, blood biochemical findings, and disease course after vitamin B1 administration were examined. This study was approved by the IRB of this institution (Approval No. 18-080). Results: Eligibility criteria were met by 76 of 126 patients who received consultations during the study period, with 32 (43%) having a vitamin B1 deficiency. Vitamin B1 treatment led to a full recovery in 19 (59%) of these 32 patients. Conclusions: Our results show that the rate vitamin B1 deficiency in patients in this study was high, although &gt;50% of the affected patients recovered with treatment. This indicated that it is necessary to pay close attention to vitamin B1 deficiency in cancer patients with psychiatric symptoms, and future study is planned to clarify the factors involved in the onset of vitamin B1 deficiency.
FDG PET/CT Course of Pembrolizumab-Associated Multiorgan Sarcoidosis
Authors: Yang Lu
Journal: Clinical Nuclear Medicine (2018)

An 80-year-old man with metastatic melanoma had been receiving treatment with pembrolizumab from September 2015 until June 2017. Series FDG PET/CT scans from March 7, 2017, to June 14, 2018, showed the course of biopsy-proven pembrolizumab-induced sarcoidosis. Reported here is the first case of multiorgan sarcoidosis induced by pembrolizumab and its self-resolving course on FDG PET/CT.
Effect of a novel vital sign device on maternal mortality and morbidity in low-resource settings: a pragmatic, stepped-wedge, cluster-randomised controlled trial
Authors: Nicola Vousden, Elodie Lawley, Hannah L Nathan, Paul T Seed, Muchabayiwa Francis Gidiri, Shivaprasad Goudar, Jane Sandall, Lucy C Chappell, Andrew H Shennan, Monice Kachinjika, Doreen Bukani, Jane Makwakwa, Grace Makonyola, Adrian Brown, Paul Toussaint, Adeline Vixama, Grace Greene, Carwyn Hill, Emily Nakiriija, Doreen Birungi, Noela Kalyowa, Dorothy Namakula, Josaphat Byamugisha, Annettee Nakimuli, Nathan Mackayi Odeke, James Ditai, Julius Wandabwa, Fatmata Momodou, Margaret Sesay, Patricia Sandi, Jeneba Conteh, Jesse Kamara, Matthew Clarke, Rebecca Best, Josephine Miti, Mercy Kopeka, Bellington Vwalika, Martina Chima, Thokozile Musonda, Christine Jere, Sebastian Chinkoyo, Violet Mambo, Yonas Guchale, Lomi Yadeta, Feiruz Surur, Geetanjali M Mungarwadi, Sphoorthi S Mastiholi, Chandrappa C Karadiguddi, Umesh Charantimath, Mrutyunjaya Bellad, Natasha Hezelgrave, Kate E Duhig
Journal: The Lancet Global Health (2019)

In 2015, an estimated 303 000 women died in pregnancy and childbirth. Obstetric haemorrhage, sepsis, and hypertensive disorders of pregnancy account for more than 50% of maternal deaths worldwide. There are effective treatments for these pregnancy complications, but they require early detection by measurement of vital signs and timely administration to save lives. The primary aim of this trial was to determine whether implementation of the CRADLE Vital Sign Alert and an education package into community and facility maternity care in low-resource settings could reduce a composite of all-cause maternal mortality or major morbidity (eclampsia and hysterectomy).
Whole-Brain Functional Ultrasound Imaging Reveals Brain Modules for Visuomotor Integration
Authors: Émilie Macé, Gabriel Montaldo, Stuart Trenholm, Cameron Cowan, Alexandra Brignall, Alan Urban, Botond Roska
Journal: Neuron (2018)

Highlights•Functional ultrasound enables imaging whole-brain activity during mouse behavior•Activity in 87 brain regions are modulated during the optokinetic reflex•Reflex-related regions were identified by perturbing retinal direction selectivity•A subset of these regions, all in the thalamus, are independent of eye motionSummaryLarge numbers of brain regions are active during behaviors. A high-resolution, brain-wide activity map could identify brain regions involved in specific behaviors. We have developed functional ultrasound imaging to record whole-brain activity in behaving mice at a resolution of ∼100 μm. We detected 87 active brain regions during visual stimulation that evoked the optokinetic reflex, a visuomotor behavior that stabilizes the gaze both horizontally and vertically. Using a genetic mouse model of congenital nystagmus incapable of generating the horizontal reflex, we identified a subset of regions whose activity was reflex dependent. By blocking eye motion in control animals, we further separated regions whose activity depended on the reflex's motor output. Remarkably, all reflex-dependent but eye motion-independent regions were located in the thalamus. Our work identifies functional modules of brain regions involved in sensorimotor integration and provides an experimental approach to monitor whole-brain activity of mice in normal and disease states.
Mindfulness training to support advance care planning: Qualitative findings from a randomized pilot.
Authors: Shelley A. Johns, Ann H. Cottingham, Tayler Gowan, Tasneem L. Talib, Patrick V. Stutz, Micah T. Faidley, Saneta M. Maiko
Journal: Journal of Clinical Oncology (2018)

4 Background: Emotional discomfort talking about end of life (EOL) often inhibits advance care planning (ACP). Mindfulness meditation facilitates emotional regulation through present-centered awareness and non-reactive coping and may help adults with cancer and their family caregivers (CGs) approach ACP with greater ease. As part of a randomized pilot study of a mindfulness intervention, we conducted qualitative interviews with cancer patients and their CGs to explore participants’ perceptions of the effects of mindfulness on EOL discussions and ACP. Methods: Adults with advanced solid malignancies and an estimated prognosis of &lt; 12 months were randomized with their CG (N = 55 dyads) to receive standard care alone or standard care plus a 6-session mindfulness intervention that included guided mindfulness meditation, mindful communication practices, and ACP information. A subset of mindfulness patients (n = 20) and CGs (n = 15) completed semi-structured qualitative interviews post-intervention that were recorded, transcribed, and coded using a deductive approach. Results: Researchers identified three primary themes. For patients and CGs, the mindfulness intervention: (1) enhanced awareness and discussion of ACP; (2) increased acceptance of poor prognosis; and (3) fostered supportive communication. Consistent with these themes, patients noted that the intervention enabled them to begin to accept that cure may not be possible, helped them “get over the hurdle” of talking about EOL, and provided an opportunity to reflect on their life priorities, including goals of care. CGs reported that the intervention fostered ACP conversations that had been previously avoided, enhanced understanding of patient preferences that often differed from their own, and increased ability to accept realities of the patient’s illness. Patients and CGs both reported improved understanding of the need to plan for EOL, greater openness to discussing sensitive issues, and an enhanced ability to listen more deeply and communicate with greater kindness. Conclusions: Findings support the use of mindfulness training to equip patients and CGs for timely EOL discussions and ACP. Clinical trial information: NCT03257007.
Associated malignancies in vulvar Paget disease
Authors: M. van der Linden, M.S. Schuurman, J. Bulten, L.F.A.G. Massuger, J. IntHout, M.A. van der Aa, J.A. de Hullu
Journal: British Journal of Dermatology (2018)

Vulvar Paget disease (VPD) is a rare skin disorder, most commonly seen in postmenopausal white women, causing patches of itching or burning skin around the vulva. There are different types, and in the past, all types of VPD were associated with breast, intestinal and urological malignancies (e.g. cancers). This study, from the Netherlands, looks at cutaneous non‐invasive VPD, which at the time of diagnosis just affects the skin. The researchers wanted to see if this type does indeed increase the risk of developing breast, intestinal or urological malignancies in comparison with the general population (people without VPD), and moreover to evaluate whether all patients with VPD should be routinely screened for malignancies. Data on the oncological (cancer) history of patients with any type of VPD between 2000 and 2015 were obtained from a nationwide archive of pathology reports in the Netherlands. Follow‐up data and a control group from the general population were obtained from the Netherlands Cancer Registry. Of the patients with VPD, 76.9% were diagnosed with cutaneous non‐invasive VPD. The researchers found that, while other types of VPD may be linked with malignancies, the group with cutaneous non‐invasive VPD had no increased risk for developing malignancies of the breast, intestine or urological tract. This suggests that routine screening for these malignancies in patients diagnosed with cutaneous non‐invasive VPD may not be necessary.
Abstract P069: Serum Uric Acid Trajectories and Type 2 Diabetes and Hypertension in Middle Age
Authors: Hao Ma, Xuan Wang, Xiang Li, Xiaoyu Guo, Lu Qi, Ying Li
Journal: Circulation (2018)

Objective: To identify SUA level trajectories throughout 12 years and to examine their associations with incident diabetes and hypertension among middle-aged men and women. Methods: A total of 7187 participants from the Mudanjiang Chronic Non-communicable Diseases Study, who were aged 30-60 years and without diabetes or hypertension at baseline, were included. The participants were followed for an average of 10.5 years by annual examinations. Latent mixture modeling was used to identify trajectories of SUA over time. Results: Consistently among women and men, five distinct trajectories of SUA were identified: low-stable, low-increasing, moderate-stable, moderate-increasing, and high-stable. In multivariate models, compared with low-stable group, for women, the adjusted hazards ratio of diabetes was 2.11 (95%CI 1.08-4.23) in the low-increasing group, 1.78 (0.81-3.92) in the moderate-stable group, 2.01 (1.02-3.97) in the moderate-increasing group, 3.00 (1.55-5.83) in the high-stable group, whereas no association was found among men. In addition, compared with low-stable group, all other trajectory groups had an increased risk of hypertension in both men and women, except for moderate-stable group in women. Participants in the moderate-increasing group exhibited the highest risk of hypertension (for women, 2.42 [1.72-3.39], for men, 2.57 [2.05-3.24]). Further adjustment for weight change during follow-up period completely ablated the trajectories-diabetes associations, except for the high-stable group in women, but the trajectories-hypertension associations remained significant in each group. Conclusions: We found that a persistent elevated or an increasing trend of SUA levels was significant associated with an increased risk of hypertension among middle-aged women and men; only persistently high UA level was associated with diabetes among women.
Unravel Inter-Tumor and Intra-Tumor Heterogeneity of Digitally Sorted Single Hodgkin and Reed Sternberg Cells Using Genome-Wide Copy Number Profiling
Authors: Chiara Mangano, Petrini Edoardo, Marianna Garonzi, Rossana Lanzellotto, Francesca Marzia Papadopulos, Chiara Bolognesi, Genny Buson, Alberto Ferrarini, Claudio Forcato, Giovanni Martinelli, Francesca Fontana, Michela Ceccolini, Francesco Fabbri, Pietro Fici, Giulia Gallerani, Cecilia Simonelli, Gianni Medoro, Nicolò Manaresi
Journal: Blood (2018)
FRI0205 Clues to systemic sclerosis sine scleroderma
Authors: I Rosner, G Slobodin, M Rozenbaum, JE Naschitz, E Toubi, A Kessel, D Yeshurun
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There is substantial difficulty in the diagnosis of progressive systemic sclerosis where visceral involvement precedes cutaneous expression of the disease. <h3>Objectives</h3> To describe clues to the diagnosis of progressive systemic sclerosis sine scleroderma (ssSSc). <h3>Methods</h3> Report of 3 cases and review of the MEDLINE database concerning ssSSc. <h3>Results</h3> Tweny five patients from the literature and 3 from our unit fulfilled the inclusion criteria, 13 females and 15 males, mean age 51.2(SD17.2) years. Conditions motivating the search for ssSSc were pulmonary fibrosis (44%), congestive heart failure (19%), esophageal dysfunction (7%), malabsorption (11%), nephropathy (11%), fever of unknown origin (3.5%) and seizures (3.5%). An overt undifferentiated connective tissue disease was present in 7 pts. Multisystem involvement became apparent when carefully searched for in all but one patient. ANA and RF were found in 13 of 17 and “scleroderma pattern” was noted in 9 of 13 patients on nailfold capillaroscopy. Taut skin developed later in 57% of pts following extracutaneous presentation by 1 month to 7 yrs (mean 2.3 yrs). <h3>Conclusion</h3> Clues to the diagnosis of ssSSc can be classified as: 1) background conditions – unclassified system disorder, Raynaud’s, polyarthritis 2) evolving visceropathy of obscure provenience – dysphagia, malabsoption, pulmonary fibrosis, heart failure, nephropathy 3) corroborative laboratory and clinical features – hyper/hypopigmentation, telangiectasis, calcinosis, typical nailfold capillaroscopy 4) confirmatory evidence – visceral biopsy, appearance of taut skin.
A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers
Authors: Joshua K Sabari, Michael Offin, Dennis Stephens, Andy Ni, Adrian Lee, Nick Pavlakis, Stephen Clarke, Connie I Diakos, Sutirtha Datta, Nidhi Tandon, Andres Martinez, Mackenzie L Myers, Alex Makhnin, Ysleni Leger, Helena A Yu, Paul K Paik, Jamie E Chaft, Mark G Kris, Jeong O Jeon, Laetitia A Borsu, Marc Ladanyi, Maria E Arcila, Jennifer Hernandez, Samantha Henderson, Tristan Shaffer, Kavita Garg, Dan DiPasquo, Christopher K Raymond, Lee P Lim, Mark Li, Matthew D Hellmann, Alexander Drilon, Gregory J Riely, Valerie W Rusch, David R Jones, Andreas Rimner, Charles M Rudin, James M Isbell, Bob T Li
Journal: JNCI Journal of the National Cancer Institute (2018)

Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use.Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided.Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96.1% (49/51, 95% CI = 86.5% to 99.5%), and directly led to matched targeted therapy in 21.9% (46/210) with clinical response.Plasma ctDNA NGS detected a variety of oncogenic drivers with a shorter TAT compared with tissue NGS and matched patients to targeted therapy with clinical response. Positive findings on plasma NGS were highly concordant with tissue NGS and can guide immediate therapy; however, a negative finding in plasma requires further testing. Our findings support the potential incorporation of plasma NGS into practice guidelines.
Osteoporosis
Authors: Sue Shapses
Journal: Annals of Internal Medicine (2018)

Letters20 February 2018OsteoporosisSue Shapses, PhD, RDNSue Shapses, PhD, RDNRutgers University, New Brunswick, New Jersey (S.S.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0586 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I thank Ensrud and Crandall (1) for their comprehensive and excellent update on osteoporosis. However, I would like to clarify the section on calcium intake recommendations (2, 3). The upper level of calcium intake is 2500 mg/d for adults up to 50 years of age but only 2000 mg/d in women and men older than 50 years because of evidence of increased risk for kidney stones. That some patients are overzealous and consume excess supplements without regard for potential adverse effects is a common problem in the field of micronutrient supplements. This can be true for calcium ...References1. Ensrud KE, Crandall CJ. In the clinic: Osteoporosis. Ann Intern Med. 2017;167:ITC17-32. [PMID: 28761958]. doi:10.7326/AITC201708010 LinkGoogle Scholar2. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-8. [PMID: 21118827] doi:10.1210/jc.2010-2704 CrossrefMedlineGoogle Scholar3. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Pr; 2011. Google Scholar Author, Article, and Disclosure InformationAffiliations: Rutgers University, New Brunswick, New Jersey (S.S.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0586. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOsteoporosis Kristine E. Ensrud and Carolyn J. Crandall Osteoporosis Kristine E. Ensrud and Carolyn J. Crandall Metrics 20 February 2018Volume 168, Issue 4Page: 306KeywordsCalciumDisclosureKidney stonesMicronutrientsOsteoporosisVitamin D ePublished: 20 February 2018 Issue Published: 20 February 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...