tbuckley/cabot-search huggingface dataset:
Combined 68Ga-DOTATOC and 18F-FDG PET Predicts a Double Component With Different Grade of a Pancreatic Neuroendocrine Tumor in a Patient With Multiple Endocrine Neoplasia Type 1
Authors: Anne-Cécile Paepegaey, Sébastien Gaujoux, Céline Meyer, Alexandre Rouquette, Rossella Libé
Journal: Clinical Nuclear Medicine (2020)

Abstract Managing decisions of pancreatic neuroendocrine tumors (pNETs) can be challenging because of different clinical presentations and prognosis. A 31-year-old woman with multiple endocrine neoplasia type 1, including a suspicious pNET, was assessed with 68 Ga-DOTATOC and 18 F-FDG PET. A high 68 Ga-DOTATOC uptake was visualized in the entire pNET, whereas a high 18 F-FDG PET uptake was present only in the upper part of the tumor. After surgery, pathology confirmed the pNET with a double component: an upper grade 2 with a Ki67 of 11% with the high 18 F-FDG PET uptake, and a lower grade 1 with a Ki67 of 2%. Combined 68 Ga-DOTATOC/ 18 F-FDG PET predicts the grade in heterogeneous pNETs.
Withaferin A, a constituent of Indian Ayurvedic medicinal plant Withania somnifera, causes G2 phase and mitotic arrest in human breast cancer cells
Authors: Silvia Stan, Yan Zeng, Shivendra Singh
Journal: Cancer Research (2008)

1262  Withaferin A is a natural compound derived from the medicinal plant Withania somnifera L., which has been safely used for centuries in the Indian traditional (Ayurvedic) medicine practice for treatment of various disorders, including neurological disorders, inflammatory conditions or as a tonic to improve the overall health. The root extract of Withania somnifera L. is available over the counter in the United States as a dietary supplement. Withaferin A has recently generated a great deal of research interest as a potential anti-cancer agent with diverse pharmacological effects, including inhibition of nuclear factor-kappaB activation, inhibition of tumor proteasome, anti-angiogenic effect, induction of protein kinase C-dependent and Par 4-dependent apoptosis, and disruption of F-actin organization. Despite these advances, however, the mechanism for anti-proliferative effect of withaferin A is not fully understood. We now demonstrate that withaferin A effectively suppresses growth of both estrogen-independent (MDA-MB-231) and estrogen-responsive (MCF-7) human breast cancer cell lines in a dose- and time-dependent manner by causing G2/M phase cell cycle arrest as revealed by flow cytometry following staining with propidium iodide. The withaferin A treated MDA-MB-231 and MCF-7 cells were also arrested in mitosis as evidenced by fluorescence microscopy following staining with anti-alpha tubulin antibody and DAPI, increased Ser-10 phosphorylation of histone H3 and hyperphosphorylation of securin. The withaferin A-mediated G2/M phase cell cycle arrest was (a) relatively more pronounced in MCF-7 cells (wild-type p53) than in the mutant p53 expressing cell line MDA-MB-231, (b) irreversible, (c) accompanied by a decrease in both G0/G1 and S phase cells, and (d) associated with a decrease in levels of proteins involved in the regulation of G2/M transition including cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C. The net result of these effects was accumulation of Tyr-15 phosphorylated (inactive) Cdk1. The withaferin A-mediated cell cycle arrest correlated with generation of reactive oxygen species in both cell lines. However, the G2/M phase cell cycle arrest caused by withaferin A was minimally affected in the presence of Euk134, a combined superoxide dismutase and catalase mimetic. In conclusion, the present study demonstrates, for the first time, that withaferin A treatment causes G2 phase and mitotic arrest in human breast cancer cells. The cell cycle arrest may be an important mechanism in growth suppressive effect of withaferin A, at least in human breast cancer cells. This investigation was supported by the NCI grant CA129347.
Self-Contained Neuromusculoskeletal Arm Prostheses
Authors: Max Ortiz-Catalan, Enzo Mastinu, Paolo Sassu, Oskar Aszmann, Rickard Brånemark
Journal: New England Journal of Medicine (2020)

We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.).
Donning a New Approach to the Practice of Gastroenterology: Perspectives From the COVID-19 Pandemic Epicenter
Authors: Amrita Sethi, Arun Swaminath, Melissa Latorre, Daniel S. Behin, Daniela Jodorkovsky, Delia Calo, Olga Aroniadis, Anjali Mone, Robin B. Mendelsohn, Reem Z. Sharaiha, Tamas A. Gonda, Lauren G. Khanna, Juan Carlos Bucobo, Satish Nagula, Sammy Ho, David L. Carr-Locke, David H. Robbins
Journal: Clinical Gastroenterology and Hepatology (2020)
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
Authors: Melissa M. Arons, Kelly M. Hatfield, Sujan C. Reddy, Anne Kimball, Allison James, Jesica R. Jacobs, Joanne Taylor, Kevin Spicer, Ana C. Bardossy, Lisa P. Oakley, Sukarma Tanwar, Jonathan W. Dyal, Josh Harney, Zeshan Chisty, Jeneita M. Bell, Mark Methner, Prabasaj Paul, Christina M. Carlson, Heather P. McLaughlin, Natalie Thornburg, Suxiang Tong, Azaibi Tamin, Ying Tao, Anna Uehara, Jennifer Harcourt, Shauna Clark, Claire Brostrom-Smith, Libby C. Page, Meagan Kay, James Lewis, Patty Montgomery, Nimalie D. Stone, Thomas A. Clark, Margaret A. Honein, Jeffrey S. Duchin, John A. Jernigan
Journal: New England Journal of Medicine (2020)

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.MethodsWe conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.ResultsTwenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide.ConclusionsRapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
Doctors can fulfil euthanasia request if patient develops dementia, rules Dutch Supreme Court
Authors: Tony Sheldon
Journal: BMJ (2020)

The Dutch Supreme Court this week ruled that a doctor may act on a previously written euthanasia request and end the life of a patient who, because of advanced dementia, can no longer express their wishes.

Doctors must, however, still adhere to criteria of care for euthanasia practice if they are to avoid prosecution. These, enshrined in the 2002 law, include that the patient is suffering “hopelessly and unbearably” and that the request is “voluntary and well considered,” meaning that the patient must be competent when the request was made.

The court judgment included “starting points,” elaborating the care criteria for doctors faced with these “exceptional” circumstances. …
New synthetic Epothilone Derivative ZK-EPO inhibits breast cancer metastasis
Authors: Jens Hoffmann, Bernd Buchmann, Wolfgang Schwede, Werner Skuballa, Rosemarie B. Lichtner, Hubertus Pietsch, Ulrich Klar
Journal: Cancer Research (2005)

3424  Epothilones represent a novel class of natural products which stabilize microtubules. Some of these natural products as well as their synthetic analogs have shown promising activity in experimental preclinical cancer studies and in cancer patients. Based on a broad fully synthetic drug optimization program with more than 350 synthesized analogs, we have developed ZK-EPO, a new derivative with outstanding preclinical efficacy. In contrast to other tubulin targeting drugs (i.e.paclitaxel), ZK-EPO is rapidly taken up by the tumor cells and preferentially accumulates in the cell nucleus. ZK-EPO inhibits the growth of a wide range of different human cancer cell lines, and, unlike paclitaxel, also suppresses the growth of cell lines that over-express P-glycoprotein at sub-nanomolar concentrations. We have shown that this epothilone is not recognized by cellular efflux mechanisms. Dose response studies with in vivo xenograft cancer models either sensitive or intrinsically resistant to paclitaxel demonstrated strong antiproliferative activity and a large therapeutic window of ZK-EPO. This broad preclinical activity spectrum provides strong evidence, that the novel epothilone analogue ZK-EPO may have antitumor efficacy in a variety of rather chemoresistant cancer indications and the compound is therefore currently being investigated in patients with different solid tumors. Breast cancer frequently metastasizes to the bones. Treatment of bone metastases is still a challange in the treatment of breast cancer. We have evaluated ZK-EPO in a breast cancer metastasis model in nude mice for palliative and adjuvant treatment. Results from these experiments demonstrated that ZK-EPO is active against bone metastases.
NLRC4 inflammasome activation is NLRP3- and phosphorylation-independent during infection and does not protect from melanoma
Authors: Jeannette L. Tenthorey, Roberto A. Chavez, Thornton W. Thompson, Katherine A. Deets, Russell E. Vance, Isabella Rauch
Journal: The Journal of Experimental Medicine (2020)

The NAIP/NLRC4 inflammasome is a cytosolic sensor of bacteria that activates caspase-1 and initiates potent immune responses. Structural, biochemical, and genetic data demonstrate that NAIP proteins are receptors for bacterial ligands, while NLRC4 is a downstream adaptor that multimerizes with NAIPs to form an inflammasome. NLRC4 has also been proposed to suppress tumor growth, though the underlying mechanism is unknown. Further, NLRC4 is phosphorylated on serine 533, which was suggested to be critical for its function. In the absence of S533 phosphorylation, it was proposed that another inflammasome protein, NLRP3, can induce NLRC4 activation. We generated a new Nlrc4-deficient mouse line and mice with S533D phosphomimetic or S533A nonphosphorylatable NLRC4. Using these models in vivo and in vitro, we fail to observe a requirement for phosphorylation in NLRC4 inflammasome function. Furthermore, we find no role for NLRP3 in NLRC4 function, or for NLRC4 in a model of melanoma. These results clarify our understanding of the mechanism and biological functions of NAIP/NLRC4 activation.
The importance of differentiating between mycosis fungoides with CD30-positive large cell transformation and mycosis fungoides with coexistent primary cutaneous anaplastic large cell lymphoma
Authors: Crystal Gao, Christopher J. McCormack, Carrie van der Weyden, Robert Twigger, Odette Buelens, Stephen Lade, Christine Khoo, Belinda A. Campbell, Michelle Goh, Penny McKelvie, H. Miles Prince
Journal: Journal of the American Academy of Dermatology (2020)
Placebo effects in allergen immunotherapy—An EAACI Task Force Position Paper
Authors: Oliver Pfaar, Ioana Agache, Karl‐Christian Bergmann, Carsten Bindslev‐Jensen, Jean Bousquet, Peter S. Creticos, Philippe Devillier, Stephen R. Durham, Peter Hellings, Susanne Kaul, Jörg Kleine‐Tebbe, Ludger Klimek, Lars Jacobsen, Marek Jutel, Antonella Muraro, Nikolaos G. Papadopoulos, Winfried Rief, Glenis K. Scadding, Manfred Schedlowski, Mohamed H. Shamji, Gunter Sturm, Ronald van Ree, Carmen Vidal, Stefan Vieths, Bettina Wedi, Roy Gerth van Wijk, Anthony J. Frew
Journal: Allergy (2020)

Abstract The placebo (Latin “I will please”) effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients’ expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double‐blind, placebo‐controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
Corkscrew Esophagus in Achalasia
Authors: Samuel Han, Mihir S Wagh
Journal: New England Journal of Medicine (2020)

An 83-year-old woman presented with dysphagia, regurgitation, and postprandial chest pain. A barium esophagram showed a corkscrew appearance of the esophagus. Findings on esophageal manometry were consistent with type III (spastic) achalasia.
LUBAC accelerates B-cell lymphomagenesis by conferring resistance to genotoxic stress on B cells
Authors: Tomoyasu Jo, Momoko Nishikori, Yasunori Kogure, Hiroshi Arima, Katsuhiro Sasaki, Yoshiteru Sasaki, Tomoko Nakagawa, Fumie Iwai, Shuji Momose, Aki Shiraishi, Hiroshi Kiyonari, Noritaka Kagaya, Tetsuo Onuki, Kazuo Shin-ya, Minoru Yoshida, Keisuke Kataoka, Seishi Ogawa, Kazuhiro Iwai, Akifumi Takaori-Kondo
Journal: Blood (2020)
Alteplase Inhibits Nerinetide, a Novel Stroke Drug
Authors: Anita Slomski
Journal: JAMA (2020)

The investigational neuroprotectant nerinetide did not reduce disability in all patients with ischemic stroke who were treated with endovascular thrombectomy, a trial in The Lancet reported. However, patients who were not concurrently treated with alteplase had a large benefit from nerinetide.
Abstract 16040: Socioeconomic Mediators of Racial and Ethnic Disparities in Congenital Heart Disease Outcomes -- A Population Based Study in California
Authors: Shabnam Peyvandi, Martina A Steurer, Rebecca Baer, Scott P Oltman, Christina D Chambers, Mary E Norton, Satish Rajagopal, Kelli K Ryckman, Anita J Moon-Grady, Laura L Jelliffe-Pawlowski
Journal: Circulation (2017)

Introduction: Despite advances in healthcare, racial/ethnic and socioeconomic (SE) disparities continue to exist in outcomes for children with congenital heart disease (CHD). We sought to determine...
John Ridley Pattison: the “man who wouldn’t lie” who chaired the government’s advisory committee on BSE
Authors: John Illman
Journal: BMJ (2020)

In 1995 the government appointed John Pattison chair of its advisory committee on bovine spongiform encephalopathy (BSE). Dubbed “the man who couldn’t lie,” Pattison was recommended by agriculture minister Douglas Hogg as someone the public could trust when they no longer trusted politicians. His success was such that, remarkably, he was knighted in 1998, after only three years in office.

Pattison evolved into a model scientific expert at a critical time. BSE had become one of the biggest public health crises since the second world war. Public concern and awareness spread more rapidly than the disease itself, fuelled by the knowledge that it was incurable and that any meat eater could catch it. More than 150 people died from Creutzfeldt-Jakob disease, the human variant of BSE, starting with 19 year old Stephen Churchill in 1995. The National Audit Office reported that the cost of BSE between 1996 and 2000 was £3.4 bn (€3.9bn; $4.3bn) and included the slaughter of 2.6 million animals.

The total cost of BSE to the UK economy exceeded £740m, according to one estimate.

In the early 1990s the government had tried but failed to convince …
Association of Delaying School Start Time With Sleep Duration, Timing, and Quality Among Adolescents
Authors: Rachel Widome, Aaron T. Berger, Conrad Iber, Kyla Wahlstrom, Melissa N. Laska, Gudrun Kilian, Susan Redline, Darin J. Erickson
Journal: JAMA Pediatrics (2020)

Sleep is a resource that has been associated with health and well-being; however, sleep insufficiency is common among adolescents.To examine how delaying school start time is associated with objectively assessed sleep duration, timing, and quality in a cohort of adolescents.This observational cohort study took advantage of district-initiated modifications in the starting times of 5 public high schools in the metropolitan area of Minneapolis and St Paul, Minnesota. A total of 455 students were followed up from grade 9 (May 3 to June 3, 2016) through grade 11 (March 15 to May 21, 2018). Data were analyzed from February 1 to July 24, 2019.All 5 participating schools started early (7:30 am or 7:45 am) at baseline (2016). At follow-up 1 (2017) and continuing through follow-up 2 (2018), 2 schools delayed their start times by 50 and 65 minutes, whereas 3 comparison schools started at 7:30 am throughout the observation period.Wrist actigraphy was used to derive indices of sleep duration, timing, and quality. With a difference-in-difference design, linear mixed-effects models were used to estimate differences in changes in sleep time between delayed-start and comparison schools.A total of 455 students were included in the analysis (among those identifying sex, 225 girls [49.5%] and 219 boys [48.1%]; mean [SD] age at baseline, 15.2 [0.3] years). Relative to the change observed in the comparison schools, students who attended delayed-start schools had an additional mean 41 (95% CI, 25-57) objectively measured minutes of night sleep at follow-up 1 and 43 (95% CI, 25-61) at follow-up 2. Delayed start times were not associated with falling asleep later on school nights at follow-ups, and students attending these schools had a mean difference-in-differences change in weekend night sleep of -24 (95% CI, -51 to 2) minutes from baseline to follow-up 1 and -34 (95% CI, -65 to -3) minutes from baseline to follow-up 2, relative to comparison school participants. Differences in differences for school night sleep onset, weekend sleep onset latency, sleep midpoints, sleep efficiency, and the sleep fragmentation index between the 2 conditions were minimal.This study found that delaying high school start times could extend adolescent school night sleep duration and lessen their need for catch-up sleep on weekends. These findings suggest that later start times could be a durable strategy for addressing population-wide adolescent sleep deficits.
PET/CT in Evaluation of Low Backache Due to Sacral Nerve Root Involvement
Authors: Divya Yadav, Meivel Angamuthu, T. Kishan Subudhi, Chandan J. Das, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Abstract Low back pain with radiation to lower limbs is due to nerve root impingement or involvement in most cases. 18 F-FDG PET/CT has shown sacral nerve root involvement in several peripheral nerve pathologies, including neurolymphomatosis, peripheral nerve sheath tumor, and plexopathies. We present 2 cases of a low back pain with ulcerative colitis and metastatic neuroendocrine tumor who underwent 18 F-FDG PET/CT and 68 Ga-DOTANOC PET/CT, respectively. PET/CT can be used as an adjunct tool to evaluate sacral nerve root involvement to look for malignant or inflammatory nerve involvement.
Two for one with split- or co-ventilation at the peak of the COVID-19 tsunami: is there any role for communal care when the resources for personalised medicine are exhausted?
Authors: Steven Dale Pearson, Jesse B Hall, William F Parker
Journal: Thorax (2020)

The international pandemic of coronavirus disease 2019 (Covid-19) has caused unprecedented strain on healthcare systems worldwide and threatens to deplete the available supply of mechanical ventilators. In addition to ventilator allocation protocols, a potential way of addressing this problem is ventilator sharing, also termed split- or co-ventilation, a concept that has gained recent attention in anticipation of dire equipment shortages. Co-ventilation was initially proposed by Neyman and Irvin in 2006 as a method of increasing surge capacity needs during disasters resulting in mass casualty respiratory failure. They demonstrated the technical feasibility of using one ventilator on four mechanical lungs, and proposed use as a last resort only after depletion of ventilators and staff available for manual ventilation to temporarily bridge to the arrival of disaster relief.1 Similar circuits have since been used in both sheep models and more sophisticated mechanical lung models.2 3 Tonetti and colleagues describe a simple circuit which can be used to ventilate two patients with one ventilator and report on its use in mechanical lung models of differing compliance and resistance.4 While this report again demonstrates the technical feasibility of ventilating multiple patients with a single ventilator, there are many areas of caution to consider before widespread implementation of this technique in the current pandemic.

Tonetti and colleagues, as well as the protocol recently published by New York Presbyterian Hospital, have attempted to address many of the technical challenges of co-ventilation, although many still remain.4 5 Front and centre among these problems is the inability to titrate mechanical ventilation to the individual patient physiology. Close matching of ventilatory settings—such as minute ventilation, positive end-expiratory pressure and fraction of inspired oxygen—to patient characteristics such as pulmonary mechanics (static compliance, resistance); oxygen consumption and carbon dioxide production; acid-base balance; and haemodynamics—is necessary to optimise …