tbuckley/cabot-search huggingface dataset:
Blocking Short-Form Ron Eliminates Breast Cancer Metastases through Accumulation of Stem-Like CD4+ T Cells That Subvert Immunosuppression
Authors: Shu-Chin Alicia Lai, Harika Gundlapalli, H. Atakan Ekiz, Amanda Jiang, Elvelyn Fernandez, Alana L. Welm
Journal: Cancer Discovery (2021)

Immunotherapy has potential to prevent and treat metastatic breast cancer, but strategies to enhance immune-mediated killing of metastatic tumors are urgently needed. We report that a ligand-independent isoform of Ron kinase (SF-Ron) is a key target to enhance immune infiltration and eradicate metastatic tumors. Host-specific deletion of SF-Ron caused recruitment of lymphocytes to micrometastases, augmented tumor-specific T-cell responses, and nearly eliminated breast cancer metastasis in mice. Lack of host SF-Ron caused stem-like TCF1+ CD4+ T cells with type I differentiation potential to accumulate in metastases and prevent metastatic outgrowth. There was a corresponding increase in tumor-specific CD8+ T cells, which were also required to eliminate lung metastases. Treatment of mice with a Ron kinase inhibitor increased tumor-specific CD8+ T cells and protected from metastatic outgrowth. These data provide a strong preclinical rationale to pursue small-molecule Ron kinase inhibitors for the prevention and treatment of metastatic breast cancer. The discovery that SF-Ron promotes antitumor immune responses has significant clinical implications. Therapeutic antibodies targeting full-length Ron may not be effective for immunotherapy; poor efficacy of such antibodies in trials may be due to their inability to block SF-Ron. Our data warrant trials with inhibitors targeting SF-Ron in combination with immunotherapy. This article is highlighted in the In This Issue feature, p. 2945.
Cross-neutralization of SARS-CoV-2 B.1.1.7 and P.1 variants in vaccinated, convalescent and P.1 infected
Authors: Anna Gidari, Samuele Sabbatini, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Claudia Monari, Barbara Luciani Pasqua, Filippo Dragoni, Elisabetta Schiaroli, Maurizio Zazzi, Daniela Francisci
Journal: Journal of Infection (2021)

The emergence of new variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) around the world significantly complicated the exit from Coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate the serum neutralizing activity of three cohorts.BNT162b2-elicited serum (N = 103), candidates as hyper-immune plasma donors (N = 90) and patients infected with the SARS-CoV-2 P1 variant (N = 22) were enrolled. Three strains of SARS-CoV-2 have been tested: 20A.EU1, B.1.1.7 (alpha) and P.1 (gamma). Neutralizing antibodies (NT-Abs) titers against SARS-CoV-2 were evaluated.B.1.1.7 and P.1 are less efficiently neutralized by convalescent wild-type infected serums if compared to 20A.EU1 strain (mean titer 1.6 and 6.7-fold lower respectively). BNT162b2 vaccine-elicited human sera show an equivalent neutralization potency on the B.1.1.7 but it is significantly lower for the P.1 variant (mean titer 3.3-fold lower). Convalescent P.1 patients are less protected from other SARS-CoV-2 strains with an important reduction of neutralizing antibodies against 20A.EU1 and B.1.1.7, about 12.2 and 10.9-fold, respectively.BNT162b2 vaccine confers immunity against all the tested VOCs, while previous SARS-CoV-2 infection may be less protective.
Treatment patterns and outcomes in elderly patients with newly diagnosed multiple myeloma: results from the Connect® MM Registry
Authors: Hans C. Lee, Sikander Ailawadhi, Cristina J. Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G. M. Durie, Mohit Narang, Howard R. Terebelo, Kathleen Toomey, James W. Hardin, Lynne Wagner, James L. Omel, Mazaher Dhalla, Liang Liu, Prashant Joshi, Rafat Abonour, Rafat Abonour
Journal: Blood Cancer Journal (2021)
Tumor Associated Macrophages and TAMs‐Based Anti‐Tumor Nanomedicines
Authors: Yuxi Cheng, Siyang Song, Peiyao Wu, Bochen Lyu, Mengmeng Qin, Yanan Sun, Aning Sun, Limin Mu, Fei Xu, Lu Zhang, Jiancheng Wang, Qiang Zhang
Journal: Advanced Healthcare Materials (2021)

As an important part of tumor microenvironment, tumor associated macrophages (TAMs) play a vital role in the occurrence, development, invasion, and metastasis of many malignant tumors and can significantly promote the formation of tumor blood vessels and lymphatic vessels, hence TAMs are greatly associated with poor prognosis. The research on nanomedicine has achieved huge progress, and nano-drugs have been widely utilized to treat various diseases through different mechanisms. Therefore, developing nano-drugs that are based on TAMs-associated anti-tumor mechanisms to effectively suppress tumor growth is expected to be a promising research filed. This paper introduces relevant information about TAMs in terms of their origin, and their roles in tumor genesis, development and metastasis. Furthermore, TAMs-related anti-tumor nano-drugs are summarized. Specifically, a wide range of nano-drugs targeting at TAMs are introduced, and categorized according to their therapeutic mechanisms toward tumors. Additionally, various nano delivery platforms using TAMs as cell carriers which aim at inhibiting tumor growth are reviewed. These two parts elucidate that the exploration of nanomedicine is essential to the study on TAMs-related anti-tumor strategies. This review is also intended to provide novel ideas for in-depth investigation on anti-tumor molecular mechanisms and nano-drug delivery systems based on TAMs.
Correction: MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients
Authors: Patrick W. Mellors, Surendra Dasari, Mindy C. Kohlhagen, Taxiarchis Kourelis, Ronald S. Go, Eli Muchtar, Morie A. Gertz, Shaji K. Kumar, Francis. K. Buadi, Maria A. V. Willrich, John A. Lust, Prashant Kapoor, Martha Q. Lacy, David Dingli, Yi Hwa, Amie Fonder, Miriam Hobbs, Susan Hayman, Rahma Warsame, Nelson R. Leung, Yi Lin, Wilson Gonsalves, Mustaqeem Siddiqui, Robert A. Kyle, S. Vincent Rajkumar, David L. Murray, Angela Dispenzieri
Journal: Blood Cancer Journal (2021)
Lessons learnt from hydroxychloroquine/azithromycin in treatment of COVID-19
Authors: Jiuyang Xu, Bin Cao
Journal: European Respiratory Journal (2021)

<b>Solid pre-clinical investigations serve as the basis for clinical research. High quality clinical trials remain the definitive measure to evaluate an interventional therapy. Clinical decisions should be independent from media and political propaganda.</b>https://bit.ly/3iaNBsB
General practice needs rescue package to prevent burnout and preserve care, warns RCGP
Authors: Elisabeth Mahase
Journal: BMJ (2021)

General practice is at “breaking point” and needs an emergency rescue package to ensure that staff are supported and that patients receive the care they need, the Royal College of General Practitioners has said.

The college’s chair, Martin Marshall, said that even before the pandemic the job of GPs was “largely undoable” but that covid-19 had led to “unsustainable” workloads, with an estimated 14 000 GPs expected to leave frontline patient care in the next five years.

The college has produced a five point plan to save general practice and prevent GPs and other members …
O9-2 Comprehensive gene mutation profiling of ctDNA in ovarian cancer and its pathological and prognostic impact
Authors: Tomoko Noguchi, Naoyuki Iwahashi, Kazuko Sakai, Kaho Matsuda, Hitomi Matsukawa, Saori Toujima, Kazuto Nishio, Kazuhiko Ino
Journal: Annals of Oncology (2021)
Predictive models of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using nuclear morphology and tissue architecture
Authors: Haoyang Mi, Trinity J. Bivalacqua, Max Kates, Roland Seiler, Peter C. Black, Aleksander S. Popel, Alexander S. Baras
Journal: Cell Reports Medicine (2021)

Characterizing likelihood of response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is an important yet unmet challenge. In this study, a machine-learning framework is developed using imaging of biopsy pathology specimens to generate models of likelihood of NAC response. Developed using cross-validation (evaluable N = 66) and an independent validation cohort (evaluable N = 56), our models achieve promising results (65%-73% accuracy). Interestingly, one model-using features derived from hematoxylin and eosin (H&E)-stained tissues in conjunction with clinico-demographic features-is able to stratify the cohort into likely responders in cross-validation and the validation cohort (response rate of 65% for predicted responder compared with the 41% baseline response rate in the validation cohort). The results suggest that computational approaches applied to routine pathology specimens of MIBC can capture differences between responders and non-responders to NAC and should therefore be considered in the future design of precision oncology for MIBC.
P5-8 A retrospective study for the significance of second-line therapy for unresectable or recurrent biliary tract cancer
Authors: Yasuyuki Kawamoto, Yoshito Komatsu, Takahiro Yamamura, Rika Saito, Ken Ito, Shintaro Nakano, Kazuaki Harada, Satoshi Yuki, Masaki Kuwatani, Naoya Sakamoto
Journal: Annals of Oncology (2021)
Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort
Authors: Shailja Shah, Alese Halvorson, Brandon McBay, Chad Dorn, Otis Wilson, Sony Tuteja, Kyong-Mi Chang, Kelly Cho, Richard Hauger, Ayako Suzuki, Christine Hunt, Edward Siew, Michael Matheny, Adriana Hung, Robert Greevy, Christianne Roumie
Journal: Gut (2021)

How can investors construct portfolios that help them reach their goals, such as a comfortable retirement for themselves, a bequest for their children, and college education for their grandchildren? Are such portfolios on the mean–variance efficient frontier? How can advisors discuss investment risk with clients whose risk tolerance varies by goal—low for retirement and higher for bequests? These are the questions answered in this article. The authors show that advisors can help clients construct portfolios that take clients to their goals while also leaving them on the mean–variance efficient frontier. <b>TOPICS:</b>Portfolio construction, performance measurement
COVID-19 detection from audio: seven grains of salt
Authors: Harry Coppock, Lyn Jones, Ivan Kiskin, Björn Schuller
Journal: The Lancet Digital Health (2021)

COVID-19 detection from audio: seven grains of saltDigital mass testing for COVID-19 via a mobile phone application could be made possible through machine learning and its ability to identify patterns in data.][4] In this critique, we present seven major issues with this research and argue that further investigation is needed before conclusions about the detectability of COVID-19 from audio can be made.Many of these issues relate to a single question: are the learnt audio representations, which correlate with COVID-19 in the various collected datasets, truly audio biomarkers caused by COVID-19?One concern is that machine learning algorithms may simply distinguish between healthy individuals and individuals who are generally unwell, rather than detecting COVID-19 itself.Distinguishing between healthy and sick individuals is a much easier but less useful task.Although some researchers have investigated this issue, for example, by constructing tasks in which trained models classify between individuals with other respiratory related diseases and individuals with COVID-19, 2,5 no studies have been able to conclude that COVID-19 itself is truly being identified.Environmental corruption is another concern.When an audio event, such as a cough, is recorded, information about the surrounding acoustic environment is also included in the audio file.The background noise introduces a potential for bias in the audio dataset.Bias from inadvertent audio additions can exist in many forms; an example in this context could be that COVID-19 positive individuals are more likely to be indoors, perhaps in a medical setting at the time of recording, than those without COVID-19, whereas COVID-19-negative individuals are more likely to be outside or perhaps in a work place setting than those with COVID-19.Each setting has its own unique identifiable environmental audio mode.Any such association can be identified by the machine learning models, as it attempts to make a COVID-19 prediction.This bias can be subtle and, once present in the dataset, is very difficult to detect and remove.This subtlety could explain why it has not been addressed as a limitation in any of the studies so far.
P-31 Real-world efficacy and safety of trifluridine/tipiracil plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies
Authors: N. Martínez Lago, B. Alonso de Castro, R. Varela Ponte, C. Reboredo Rendo, M. Gomez-Randulfe Rodriguez, B. Graña Suarez, J. de la cámara gomez, M. Mateos Salvador, F. Busto Fernandez, T. Calleja Chucla, M. Reboredo-Lopez
Journal: Annals of Oncology (2021)
Pimavanserin in Dementia-Related Psychosis
Authors: Joseph I. Friedman
Journal: New England Journal of Medicine (2021)

Dementia occurs in a range of progressive neurodegenerative brain disorders, including Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular dementia, and frontotemporal dementia, each classified according to their respective neuropathological characteristics. Dementia is clinically defined by cognitive and functional impairments and is often associated with behavioral and psychological disturbances including psychosis. The behavioral disturbances often include aggression and agitation, and symptoms of psychosis often include delusions and hallucinations that are distressing and burdensome to patients and caregivers. Estimates of the prevalence of psychosis in dementia vary among studies, with hallucinations occurring in 15 to 50% of patients with . . .
Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma
Authors: Roberto Vendramin, Vicky Katopodi, Sonia Cinque, Angelina Konnova, Zorica Knezevic, Sara Adnane, Yvessa Verheyden, Panagiotis Karras, Ewout Demesmaeker, Francesca M. Bosisio, Lukas Kucera, Jan Rozman, Ivan Gladwyn-Ng, Lara Rizzotto, Erik Dassi, Stefania Millevoi, Oliver Bechter, Jean-Christophe Marine, Eleonora Leucci
Journal: The Journal of Experimental Medicine (2021)

The ability to adapt to environmental stress, including therapeutic insult, contributes to tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent survival also relies on a concomitant up-regulation of mitochondrial protein synthesis, a vulnerability that can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized to MAPK inhibition, thus preventing the development of resistance in BRAFV600E melanoma models. Additionally, this treatment compromised the growth of melanomas that exhibited elevated ISR activity and resistance to both immunotherapy and targeted therapy. In keeping with this, pharmacological inactivation of ISR, or silencing of ATF4, rescued the antitumoral response to the tetracyclines. Moreover, a melanoma patient exposed to doxycycline experienced complete and long-lasting response of a treatment-resistant lesion. Our study indicates that the repurposing of mitoribosome-targeting antibiotics offers a rational salvage strategy for targeted therapy in BRAF mutant melanoma and a therapeutic option for NRAS-driven and immunotherapy-resistant tumors.
Abstract 14123: Human Pentraxin 3 is a Novel Biomarker for Diagnosing Pulmonary Arterial Hypertension
Authors: Yuichi Tamura, Tomohiko Ono, Masaharu Kataoka, Toshiki Kuno, Takashi Kawakami, Kensuke Kimura, Motoaki Sano, Masataka Kuwana, Toru Satoh, Keiichi Fukuda
Journal: Circulation (2011)

[Background] Inflammation is a feature of pulmonary arterial hypertension (PAH) and levels of increased circulating interleukin 6 (IL-6) correlate with survival of patients with idiopathic PAH. Man...
Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study
Authors: Brian A. Fallon, Trine Madsen, Annette Erlangsen, Michael E. Benros
Journal: American Journal of Psychiatry (2021)

Lyme borreliosis is a tick-borne infectious disease that may confer an increased risk of mental disorders, but previous studies have been hampered by methodological limitations, including small sample sizes. The authors used a nationwide retrospective cohort study design to examine rates of mental disorders following Lyme borreliosis.Using Denmark's National Patient Register and the Psychiatric Central Research Register, and including all persons living in Denmark from 1994 through 2016 (N=6,945,837), the authors assessed the risk of mental disorders and suicidal behaviors among all individuals diagnosed with Lyme borreliosis in inpatient and outpatient hospital contacts (N=12,156). Incidence rate ratios (IRRs) were calculated by Poisson regression analyses.Individuals with Lyme borreliosis had higher rates of any mental disorder (IRR=1.28, 95% CI=1.20, 1.37), of affective disorders (IRR=1.42, 95% CI=1.27, 1.59), of suicide attempts (IRR=2.01, 95% CI=1.58, 2.55), and of death by suicide (IRR=1.75, 95% CI=1.18, 2.58) compared with those without Lyme borreliosis. The 6-month interval after diagnosis was associated with the highest rate of any mental disorder (IRR=1.96, 95% CI=1.53, 2.52), and the first 3 years after diagnosis was associated with the highest rate of suicide (IRR=2.41, 95% CI=1.25, 4.62). Having more than one episode of Lyme borreliosis was associated with increased incidence rate ratios for mental disorders, affective disorders, and suicide attempts, but not for death by suicide.Individuals diagnosed with Lyme borreliosis in the hospital setting had an increased risk of mental disorders, affective disorders, suicide attempts, and suicide. Although the absolute population risk is low, clinicians should be aware of potential psychiatric sequelae of this global disease.
A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
Authors: Brenna L. Hughes, Rebecca G. Clifton, Dwight J. Rouse, George R. Saade, Mara J. Dinsmoor, Uma M. Reddy, Robert Pass, Donna Allard, Gail Mallett, Lida M. Fette, Cynthia Gyamfi-Bannerman, Michael W. Varner, William H. Goodnight, Alan T.N. Tita, Maged M. Costantine, Geeta K. Swamy, Ronald S. Gibbs, Edward K. Chien, Suneet P. Chauhan, Yasser Y. El-Sayed, Brian M. Casey, Samuel Parry, Hyagriv N. Simhan, Peter G. Napolitano, George A. Macones
Journal: New England Journal of Medicine (2021)

Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection.
MO12-3 Association between relative dose intensity and prognosis in patients aged 80 years and older with DLBCL
Authors: Shin Lee, Kei Fujita, Tetsuji Morishita, Eiju Negoro, Kana Oiwa, Hikaru Tsukasaki, Takeshi Hara, Hisashi Tsurumi, Takanori Ueda, Takahiro Yamauchi
Journal: Annals of Oncology (2021)
MO21-1 Prognostic value of pneumonitis after durvalumab in locally-advanced non-small cell lung cancer
Authors: Ari Nishimura, Akira Ono, Kazushige Wakuda, Takanori Kawabata, Michitoshi Yabe, Taichi Miyawaki, Eriko Miyawaki, Hiroaki Kodama, Naoya Nishioka, Nobuaki Mamesaya, Haruki Kobayashi, Shota Omori, Hirotsugu Kenmostu, Tateaki Naito, Haruyuki Murakami, Hideyuki Harada, Toshiaki Takahashi
Journal: Annals of Oncology (2021)
Annual Incidence of Hospitalization for Nonfatal Firearm-Related Injuries in New York From 2005 to 2016
Authors: Yu-Tien Hsu, Ya-Wen Chen, David C. Chang, Numa P. Perez, Maggie L. Westfal, Ya-Ching Hung, Cassandra M. Kelleher, Peter T. Masiakos, Chana A. Sacks
Journal: JAMA Network Open (2021)

In the US, approximately 40 000 people die due to firearm-related injuries annually. However, nonfatal firearm-related injuries are less precisely tracked.To assess the annual incidence of hospitalization for nonfatal firearm-related injuries in New York and to compare the annual incidence by sex, race/ethnicity, county of residence, and calendar years.This retrospective cross-sectional study used data from the New York Statewide Planning and Research Cooperative System for patients aged 15 years or older who presented to an emergency department in New York with nonfatal firearm-related injuries from January 1, 2005, to December 31, 2016. Data were analyzed from January 15, 2019, to April 21, 2021.A nonfatal firearm-related injury, defined by International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes.The annual incidence of nonfatal firearm-related injuries was calculated by determining the number of patients with a nonfatal firearm-related injury each year divided by the total population of New York.The study included 31 060 unique patients with 35 059 hospital encounters for nonfatal firearm-related injuries. The mean (SD) age at admission was 28.5 (11.9) years; most patients were male (90.6%) and non-Hispanic Black individuals (62.0%). The overall annual incidence was 18.4 per 100 000 population. Although decreasing trends of annual incidence were observed across the state during the study period, this trend was not present in all 62 counties, with 32 counties (51.6%) having an increase in the incidence of injuries between 2005 and 2010 and 29 (46.8%) having an increase in the incidence of injuries between 2010 and 2015. In 19 of the 30 counties (63.3%) that had a decrease in incidence in earlier years, the incidence increased in later years.The annual incidence of hospitalization for nonfatal firearm-related injuries in New York during the study period was 18.4 per 100 000 population. Reliable tracking of nonfatal firearm-related injury data may be useful for policy makers, hospital systems, community organizers, and public health officials as they consider resource allocation for trauma systems and injury prevention programs.
Adherence to minimal experimental requirements for defining extracellular vesicles and their functions
Authors: Rodolphe Poupardin, Martin Wolf, Dirk Strunk
Journal: Advanced Drug Delivery Reviews (2021)

Rigorous measures are required to cope with the advance of extracellular vesicle (EV) research, from 183 studies published in 2012 to 2,309 studies published in 2020. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines in 2014, updated in 2018, for assuring and improving EV research quality. We performed a systematic review using a text mining approach to assess adherence to MISEV criteria. A keyword search was conducted in 5,093 accessible publications over the period 2012–2020 and analyzed the methodology used for EV isolation and characterization. We found a significant improvement over the years particularly regarding EV characterization where recent papers used a higher number of methods and EV markers to check for quantity and purity. Interestingly, we also found that EV papers using more methods and EV markers were cited more frequently. Papers citing MISEV criteria were more prone to use a higher number of characterization methods. We therefore established a concise checklist summarizing MISEV criteria to support EV researchers towards reaching the highest standards in the field.