tbuckley/cabot-search huggingface dataset:
Prognostic Significance of Cardiac 123I-MIBG SPECT Imaging in Heart Failure Patients With Preserved Ejection Fraction
Authors: Masahiro Seo, Takahisa Yamada, Shunsuke Tamaki, Tetsuya Watanabe, Takashi Morita, Yoshio Furukawa, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Takanari Kimura, Kunpei Ueda, Daisuke Sakamoto, Yasushi Sakata, Masatake Fukunami
Journal: JACC. Cardiovascular imaging (2021)
MA17.05 Intrapulmonary Lymph Node (LN) Retrieval With a Novel Gross Dissection Method: A Prospective, Population-Based Cohort Study
Authors: M. Ray, Y. Lee, N. Faris, C. Fehnel, O. Akinbobola, M. Meadows-Taylor, D. Spencer, E. Sales, S. Okun, C. Giampapa, A. Anga, A. Pacheco, M. Smeltzer, R. Osarogiagbon
Journal: Journal of Thoracic Oncology (2021)
From study to scalpel: knowledge translation for research in orthopaedic surgery
Authors: Hana Marmura, Anita Kothari, Alan MJ Getgood, Jane S Thornton, Dianne M Bryant
Journal: British Journal of Sports Medicine (2021)

Evidence-based medicine (EBM) requires current best evidence to support treatment decisions for individuals.1 Despite substantial growth in EBM, medical practice continues to lag behind best evidence, and orthopaedics is no exception. In one study, American patients were only receiving about 57% of recommended care for orthopaedic conditions, indicating a research-to-practice gap.2 Orthopaedic research investigating surgical interventions is time consuming, costly and complex. Additionally, findings must reach a wide population of surgeons and patients to have impact. Researchers commonly rely on two main channels of dissemination: journal publication and conference presentations,3 often only reaching like-minded researchers and clinicians. Knowledge translation (KT) supports EBM and is the synthesis, dissemination, exchange and ethically sound application of knowledge to improve health care.4 Strong KT plans can help secure research funding, scale up interventions, strengthen the quality of research and widen the impact of important studies. A concerted effort to improve KT within orthopaedics has the potential for rapid improvement in the field, by narrowing the knowledge to action gap, influencing decision-makers, and ultimately improving patient outcomes. This editorial will walk readers through five key steps to develop feasible and effective KT plans to disseminate evidence-based best practices in orthopaedic surgery (figure 1). The steps are structured according to John Lavis' five questions and organisation framework for effective translation of research knowledge5 (box 1). Figure 1 Five steps to creating an effective knowledge translation plan for research in orthopaedic surgery. Box 1 ### Five guiding questions for knowledge translation plans5
Assisted dying: changing the law still has an unacceptably high price
Authors: Rowan Williams
Journal: BMJ (2021)

The support of some prominent religious figures for assisted dying has added a new element to the discussion,1 but the arguments remain essentially the same. Two broader points, however, need to be made clear.

Firstly, those resisting legal change include religious believers and unbelievers alike, as well as a large proportion of those directly involved in end-of-life care and palliative medicine. Secondly, the arguments against a change in the law are routinely …
Hypermethylation and aberrant expression of galanin in human gastric cancer
Authors: Kyong-Ah Yoon, Sang Hee Lee, Hyea-Jin Gil, Kyungsil Yoon, Kyung-Hee Chun, Jin Soo Lee
Journal: Cancer Research (2008)

4295  Galanin is a 30 amino-acid active neuropeptide and functions through interaction with three G-protein coupled galanin receptors, GALR1, GALR2 and GALR3. Galanin was used as a combinational therapy trial with octreotide and serotonin in human colon cancer models and induced tumor necrosis and apoptosis (El-Salhy et al., 2004). Recently, galanin and galanin receptor type I were reported that they inhibit proliferation in human oral cancer cell lines by down-regulation of cyclinD1 and activation of the cyclin-dependent kinase inhibitors (Kanazawa et al., 2007). GALR1 was also suggested as a tumor suppressor gene that frequently silenced in head and neck squamous cell carcinoma. However, the significant role of galanin in cancer has not been sufficiently elucidated. Here, we report identification of frequent hypermethylation in CpG islands of galanin that correlates with its transcription silencing in gastric cancer. First, we examined the expression level of galanin in 10 gastric cancer cell lines, 8 breast cancer cell lines, and 12 lung cancer cell lines. Particularly in gastric cancer cell lines, five cancer cell lines (50%) such as SNU-1, SNU-601, SNU-638, KATOIII, AGS showed significant loss of galanin expression. In the genomic region of galanin, CpG island around its transcription start site was examined by methylation specific PCR. Bisulfite-treated genomic DNA was amplified by using either a methylation- or unmethylation-specific primer set. All cell lines tested lacking galanin expression were found to be hypermethylated in CpG island. In addition, we found that Galanin expression was restored after treatment with the demethylating agent 5-aza-2’-deoxycytidine in those gastric cancer cell lines lacking galanin expression. When we compared the methylation pattern of galanin in twenty gastric cancer tissues and paired normal tissues, six samples (30%) were found to show aberrant methylation in cancer tissues. The hypermethylated galanin did not affect on the expression level of its three receptors, GARL1, GARL2, GARL3. Moreover, induction of exogenous galanin into silenced cells suppressed cell proliferation. Taken together, these data suggest that epigenetic silencing by hypermethylation of the galanin CpG island leas to inactivation of galanin, which may be involved in gastric cancer carcinogenesis.
28P Validation of cytokeratin (CK18) protein expression in epithelial cell lines and in circulating tumor cells (CTCs)
Authors: N.V. Raut, N. Kale, None A. d'Souza, Y. Patil, P. Chakraborty, K. Prabhash, P. Chaturvedi, J. Khandare
Journal: Annals of Oncology (2021)
Evolutionary Implications of the RNA <i>N</i>6-Methyladenosine Methylome in Plants
Authors: Zhenyan Miao, Ting Zhang, Bin Xie, Yuhong Qi, Chuang Ma
Journal: Molecular Biology and Evolution (2021)

Abstract Epigenetic modifications play important roles in genome evolution and innovation. However, most analyses have focused on the evolutionary role of DNA modifications, and little is understood about the influence of posttranscriptional RNA modifications on genome evolution. To explore the evolutionary significance of RNA modifications, we generated transcriptome-wide profiles of N6-methyladenosine (m6A), the most prevalent internal modification of mRNA, for 13 representative plant species spanning over half a billion years of evolution. These data reveal the evolutionary conservation and divergence of m6A methylomes in plants, uncover the preference of m6A modifications on ancient orthologous genes, and demonstrate less m6A divergence between orthologous gene pairs with earlier evolutionary origins. Further investigation revealed that the evolutionary divergence of m6A modifications is related to sequence variation between homologs from whole-genome duplication and gene family expansion from local-genome duplication. Unexpectedly, a significant negative correlation was found between the retention ratio of m6A modifications and the number of family members. Moreover, the divergence of m6A modifications is accompanied by variation in the expression level and translation efficiency of duplicated genes from whole- and local-genome duplication. Our work reveals new insights into evolutionary patterns of m6A methylomes in plant species and their implications, and provides a resource of plant m6A profiles for further studies of m6A regulation and function in an evolutionary context.
Treatment of overdose in the synthetic opioid era
Authors: Phil Skolnick
Journal: Pharmacology & Therapeutics (2021)

Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".
Cervical Cancer Screening Among Medicaid Patients During Natural Disasters and the COVID-19 Pandemic in Puerto Rico, 2016 to 2020
Authors: Ana Patricia Ortiz, Axel Gierbolini-Bermúdez, Jeslie M. Ramos-Cartagena, Vivian Colón-López, Kalyani Sonawane, Ashish A. Deshmukh, Karen J. Ortiz-Ortiz
Journal: JAMA Network Open (2021)

This cohort study examines rates of cervical cancer screening in Puerto Rico among women with Medicaid health coverage following the 2017 hurricanes, earthquakes in late 2019-2020, and the 2020 COVID-19 lockdown.
Should prehospital early warning scores be used to identify which patients need urgent treatment for sepsis?
Authors: Steve Goodacre, Ben Thomas, Michael Smyth, Jon M Dickson
Journal: BMJ (2021)

### What you need to know Early recognition and treatment of sepsis is essential to reduce mortality, but this can only be achieved if patients with suspected sepsis receive priority treatment in the emergency care system. One suggested approach for identifying these patients is through the use of early warning scores. These use simple clinical measurements to calculate a score indicating the risk of adverse outcome,1 and several guidelines make recommendations around their use in early recognition of sepsis (see box 1). Box 1 ### Guidelines recommending the use of early warning scores to aid in early recognition of sepsis risk in adultsRETURN TO TEXT
Survival in patients with radiological diagnoses of glioblastoma: a retrospective study of 115 patients on a best supportive care pathway
Authors: James Riley, James Hodson, Vladimir Petrik
Journal: Neuro-Oncology (2021)

Abstract Aims Glioblastoma multiforme (GBM) is a devastating disease with notoriously poor survival. Studies examining survival in patients given best supportive care (BSC) are few and far between. All patients harbouring brain tumours referred to the Neuro-oncology service at the Queen Elizabeth Hospital in Birmingham are recorded in the Somerset Cancer Registry. We set out to analyse survival times and identify patient and tumour-related factors significantly affecting prognosis. Method We identified 126 patients from 2015 to 2019 in our Somerset Cancer Registry with radiological diagnoses of glioblastoma for whom the Neuro-oncology MDT recommended BSC. We performed a retrospective analysis of clinical records and radiological images. 11 patients were excluded (8 due to insufficient imaging data, 2 who underwent subsequent surgery, 1 patient with brain metastases). Survival was measured in completed weeks since the index MDT decision. Associations between survival time and both patient- and tumour-related factors were assessed using Kaplan-Meier curves and log-rank tests. All analyses were performed using IBM SPSS 22 (IBM Corp. Armonk, NY), with p&amp;lt;0.05 deemed to be indicative of statistical significance throughout. Results Data were available for N=115 patients (69 males, 46 females), with a mean age of 79 ± 8 years. All patients died within 32 weeks of diagnosis, with a median survival time of 8 weeks. Only 8 patients survived for more than 20 weeks. Survival was significantly shorter in those with a greater number of main cerebral structures affected (p=0.044), with a median of 6 vs. 10 weeks for 3 or more vs. 1 structures affected (hazard ratio: 1.61, 95% CI: 0.99-2.62). Bilateral tumours involving the corpus callosum were also associated with shorter survival (p=0.039). None of the other factors considered were found to be significantly associated with survival, including age (p=0.193), gender (p=0.371), performance status (p=0.300) and tumour size (p=0.331). Conclusion With the exception of the number of main cerebral structures affected (frontal, parietal, temporal and occipital lobes, corpus callosum, insula, basal ganglia and brain stem), patient- and tumour-factors traditionally used by the MDT to prognosticate do not correlate with survival time in patients receiving BSC for radiological diagnoses of GBM. With 50% of the cohort dying within 8 weeks it is clear that we must reconsider the timing of referrals to palliative and hospice care. Finally, the fact that some patients survived for more than half a year with no surgical or oncological treatment suggests that the process of selecting patients for BSC vs aggressive treatments needs refinement.
Ependymomas: surgeon case volume and patient outcomes
Authors: Rosa Sun, Naomi Slator, Andrew Kay
Journal: Neuro-Oncology (2021)

Abstract Aims Ependymomas (tumours arising from ependymal cells) are rare in the adult population and therefore there is limited class 1 evidence on the treatment and management of these patients. We present our experience from a large single center. We address whether management should be undertaken by sub-specialised surgeons with high volume experience. Method Retrospective comparative study. Results High volume surgeons operated on larger volume (16.14 mm3, 8.31mm3, p=0.10) and more complex tumours (multi-centric cases p=0.10). We find a non-significant improvement in complication rate (p=0.77), extent of gross total resection (70.8% against 65.7%) and a positive change in performance status for high volume surgeons (p=0.84). Length of hospital stay is significantly prolonged when complications occur (14.2 and 48.4 days, p&amp;lt;0.05). Conclusion Surgeons who have higher case load of ependymomas operate on more complex tumours. In addition, our results indicate there is a technical advantage of high volume surgeons compared to low volume surgeons, which translates into improved clinical outcomes for patients. We show that this has a significant impact on length of hospital stay, as well as the associated economical implications. For rare tumours such as ependymomas, super-specialisation and referral to surgeons with higher case volume will likely improve patient outcomes. We call for a multi-centre, prospective studies to combine data in demonstrating statistical significance (power calculation for complication rate, N=150, p=0.05).
P47.14 Study Design of SCORPION: Multi-Center, Phase II Study Following Platinum-Based Chemotherapy Plus ICIs in Patients with NSCLC
Authors: R. Matsuzawa, M. Morise, K. Ito, O. Hataji, K. Takahashi, T. Hara, Y. Goto, K. Imaizumi, H. Itani, T. Yamaguchi, Y. Zenke, M. Oki, Y. Kogure, N. Hashimoto
Journal: Journal of Thoracic Oncology (2021)
Trends in Electronic Health Record Inbox Messaging During the COVID-19 Pandemic in an Ambulatory Practice Network in New England
Authors: Bidisha Nath, Brian Williams, Molly M. Jeffery, Ryan O’Connell, Richard Goldstein, Christine A. Sinsky, Edward R. Melnick
Journal: JAMA Network Open (2021)

Edward R. Melnick, MD, MHS; Allan Fong, MS; Bidisha Nath, MBBS, MPH; Brian Williams, MD; Raj M. Ratwani, PhD; Richard Goldstein, MD, PhD; Ryan T. O'Connell, MD; Christine A. Sinsky, MD; Daniel Marchalik, MD; Mihriye Mete, PhD
P50.06 First-Line Therapy in NSCLC harbouring EGFR or HER2 Exon 20 Insertion Mutation. Hunting for the Best Candidate
Authors: A. Prelaj, A. Bottiglieri, G. Lo Russo, R. Ferrara, G. Galli, A. De Toma, M. Brambilla, M. Occhipinti, S. Manglaviti, T. Beninato, E. Zattarin, G. Apollonio, G. Massa, L. Mazzeo, E. Galli, D. Dumitrascu, M. Ganzinelli, R. Gallucci, R. Di Mauro, S. Vitale, F.G.M. De Braud, M.C. Garassino, C. Proto
Journal: Journal of Thoracic Oncology (2021)
A unique population of neutrophils generated by air pollutant–induced lung damage exacerbates airway inflammation
Authors: Jae Woo Shin, Jihyun Kim, Seokjin Ham, Sun Mi Choi, Chang-Hoon Lee, Jung Chan Lee, Ji Hyung Kim, Sang-Heon Cho, Hye Ryun Kang, You-Me Kim, Doo Hyun Chung, Yeonseok Chung, Yoe-Sik Bae, Yong-Soo Bae, Tae-Young Roh, Taesoo Kim, Hye Young Kim
Journal: Journal of Allergy and Clinical Immunology (2021)
Significantly reduced abilities to cross-neutralize SARS-CoV-2 variants by sera from convalescent COVID-19 patients infected by Delta or early strains
Authors: Ting Pan, Zhongwei Hu, Fengyu Hu, Yiwen Zhang, Bingfeng Liu, Changwen Ke, Qiumin She, Xin He, Xiaoping Tang, Hui Zhang
Journal: Cellular and Molecular Immunology (2021)

The worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 4.5 million deaths.Although coronaviruses have a proofreading mechanism to maintain the stability of their long genomic RNAs, mutations emerge continuously, and new variants conferring advantages rapidly become the dominant lineages [1].Strategies to fight the COVID-19 pandemic using either vaccines or nonpharmaceutical interventions have specifically been threatened by the emergence of SARS-CoV-2 variants of concern (VOCs) [2].The N501Y mutation of the viral spike (S) protein, which is found in lineages such as B.1.1.7 (Alpha strain), B.1.351(Beta strain), and P.1 (Gamma strain), increase viral transmission due to the enhanced affinity binding to ACE2 [3].The E484K/Q mutation in the spike contributes to evasion of antibody neutralization in VOCs, such as B. 1.351 and P.1 [4].The neutralizing titers of the sera from convalescent and vaccinated individuals were reduced against the Beta strain, as reported by us and others [4].Notably, a novel variant, B.1.617.2 (Delta strain), quickly spread to 135 countries and became a dominant strain in many countries as of 8 Sep 2021.The Delta strain harbors eight mutations in the S protein, including L452R and T478K in the receptor binding domain (RBD).This variant is highly transmissible and causes breakthrough infection in vaccinated people as the protection of vaccines wanes [5,6].However, the humoral immune responses of the Delta strain are largely unknown in naive and vaccinated individuals as well as convalescent patients.In this study, we collected serum samples from 26 convalescent patients who were infected with the SARS-CoV-2 Delta strain and exhibited mild or moderate symptoms during May-June 2021 in Guangzhou, Guangdong, China and hospitalized in the Guangzhou 8th People's Hospital.Some samples were sequenced to confirm that the COVID-19 pathogen was the Delta strain.Because locally infected people were quite limited in Guangzhou, Guangdong, during May-June 2021, the transmission route study clearly indicated that the rest of them were infected by the SARS-CoV-2 Delta strain.The median age of the Delta strain-infected patients was 45 years (range: 22-83 years), and 42.3% of them were
Microbial Flavonoid Metabolism: A Cardiometabolic Disease Perspective
Authors: Lucas J. Osborn, Jan Claesen, J. Mark Brown
Journal: Annual Review of Nutrition (2021)

Cardiometabolic disease (CMD) is a leading cause of death worldwide and encompasses the inflammatory metabolic disorders of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. Flavonoids are polyphenolic plant metabolites that are abundantly present in fruits and vegetables and have biologically relevant protective effects in a number of cardiometabolic disorders. Several epidemiological studies underscored a negative association between dietary flavonoid consumption and the propensity to develop CMD. Recent studies elucidated the contribution of the gut microbiota in metabolizing dietary intake as it relates to CMD. Importantly, the biological efficacy of flavonoids in humans and animal models alike is linked to the gut microbial community. Herein, we discuss the opportunities and challenges of leveraging flavonoid intake as a potential strategy to prevent and treat CMD in a gut microbe-dependent manner, with special emphasis on flavonoid-derived microbial metabolites.
Signatures of GVHD and relapse after posttransplant cyclophosphamide revealed by immune profiling and machine learning
Authors: Shannon R. McCurdy, Vedran Radojcic, Hua-Ling Tsai, Ante Vulic, Elizabeth Thompson, Sanja Ivcevic, Christopher G. Kanakry, Jonathan D. Powell, Brian Lohman, Djamilatou Adom, Sophie Paczesny, Kenneth R. Cooke, Richard J. Jones, Ravi Varadhan, Heather J. Symons, Leo Luznik
Journal: Blood (2021)
48P Low glucose sensitizes A431 skin cancer cells to metformin treatments: A way forward to targeting PD-L1
Authors: A.L. Mikhaylova, A.A. Basharina, D.V. Sorokin, G.I. Buravchenko, S.A. Samsonik, T.A. Bogush, A.M. Scherbakov
Journal: Annals of Oncology (2021)
Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma
Authors: Adolfo Aleman, Bhaskar Upadhyaya, Kevin Tuballes, Katerina Kappes, Charles.R. Gleason, Katherine Beach, Sarita Agte, Komal Srivastava, Oliver Van Oekelen, Vanessa Barcessat, Nina Bhardwaj, Seunghee Kim-Schulze, Sacha Gnjatic, Brian Brown, Carlos Cordon-Cardo, Florian Krammer, Miriam Merad, Sundar Jagannath, Ania Wajnberg, Viviana Simon, Samir Parekh, D. Andre, A. Azad, R. Banu, M.C. Bermúdez-González, G. Cai, C. Cognigni, K. David, D. Floda, A. Firpo, G. Kleiner, N. Lyttle, W. Mendez, L.C.F. Mulder, R. Mendu, A. Oostenink, A. Rooker, K. Russo, A. Salimbangon, M. Saksena, A. Shin, L. Sominsky
Journal: Cancer Cell (2021)