tbuckley/cabot-search huggingface dataset:
724MO Balstilimab (anti-PD-1) in combination with zalifrelimab (anti-CTLA-4): Final results from a phase II study in patients (pts) with recurrent/metastatic (R/M) cervical cancer (CC)
Authors: D. O'Malley, M. Neffa, B.J. Monk, T. Melkadze, A. Kryzhanivska, I.V. Bulat, T. Meniawy, I. Bondarenko, W.I. Ortuzar Feliu, M. Ancukiewicz, I. Lugowska
Journal: Annals of Oncology (2021)
36P In-vitro tonic signalling profiling of CAR-T cells generated to support pre-clinical studies for solid tumour targets
Authors: S.S. Hunjan, R. Sampson, J. Evans, H. Chenoweth, I. Garrobo-Calleja, S. Lekomtsev, J. Zhang, S. Zona, J. Breuning, R. Oren, M. Davies, A. Di-Tullio, J. Euesden, J. Kennedy, C. Kay, J. Colebrook, B.P. Kloke, T. Southgate, J. Lee
Journal: Annals of Oncology (2021)
Regional differences in short stature in England between 2006 and 2019: A cross-sectional analysis from the National Child Measurement Programme
Authors: Joanna Orr, Joseph Freer, Joan K. Morris, Caroline Hancock, Robert Walton, Leo Dunkel, Helen L. Storr, Andrew J. Prendergast
Journal: PLoS Medicine (2021)

Background Short stature, defined as height for age more than 2 standard deviations (SDs) below the population median, is an important indicator of child health. Short stature (often termed stunting) has been widely researched in low- and middle-income countries (LMICs), but less is known about the extent and burden in high-income settings. We aimed to map the prevalence of short stature in children aged 4–5 years in England between 2006 and 2019. Methods and findings We used data from the National Child Measurement Programme (NCMP) for the school years 2006–2007 to 2018–2019. All children attending state-maintained primary schools in England are invited to participate in the NCMP, and heights from a total of 7,062,071 children aged 4–5 years were analysed. We assessed short stature, defined as a height-for-age standard deviation score (SDS) below −2 using the United Kingdom WHO references, by sex, index of multiple deprivation (IMD), ethnicity, and region. Geographic clustering of short stature was analysed using spatial analysis in SaTScan. The prevalence of short stature in England was 1.93% (95% confidence interval (CI) 1.92–1.94). Ethnicity adjusted spatial analyses showed geographic heterogeneity of short stature, with high prevalence clusters more likely in the North and Midlands, leading to 4-fold variation between local authorities (LAs) with highest and lowest prevalence of short stature. Short stature was linearly associated with IMD, with almost 2-fold higher prevalence in the most compared with least deprived decile (2.56% (2.53–2.59) vs. 1.38% (1.35–1.41)). There was ethnic heterogeneity: Short stature prevalence was lowest in Black children (0.64% (0.61–0.67)) and highest in Indian children (2.52% (2.45–2.60)) and children in other ethnic categories (2.57% (2.51–2.64)). Girls were more likely to have short stature than boys (2.09% (2.07–2.10) vs. 1.77% (1.76–1.78), respectively). Short stature prevalence declined over time, from 2.03% (2.01–2.05) in 2006–2010 to 1.82% (1.80–1.84) in 2016–2019. Short stature declined at all levels of area deprivation, with faster declines in more deprived areas, but disparities by IMD quintile were persistent. This study was conducted cross-sectionally at an area level, and, therefore, we cannot make any inferences about the individual causes of short stature. Conclusions In this study, we observed a clear social gradient and striking regional variation in short stature across England, including a North–South divide. These findings provide impetus for further investigation into potential socioeconomic influences on height and the factors underlying regional variation.
The blood–brain barrier in systemic infection and inflammation
Authors: Ian Galea
Journal: Cellular and Molecular Immunology (2021)

Abstract The vascular blood–brain barrier is a highly regulated interface between the blood and brain. Its primary function is to protect central neurons while signaling the presence of systemic inflammation and infection to the brain to enable a protective sickness behavior response. With increasing degrees and duration of systemic inflammation, the vascular blood–brain barrier becomes more permeable to solutes, undergoes an increase in lymphocyte trafficking, and is infiltrated by innate immune cells; endothelial cell damage may occasionally occur. Perturbation of neuronal function results in the clinical features of encephalopathy. Here, the molecular and cellular anatomy of the vascular blood–brain barrier is reviewed, first in a healthy context and second in a systemic inflammatory context. Distinct from the molecular and cellular mediators of the blood–brain barrier’s response to inflammation, several moderators influence the direction and magnitude at genetic, system, cellular and molecular levels. These include sex, genetic background, age, pre-existing brain pathology, systemic comorbidity, and gut dysbiosis. Further progress is required to define and measure mediators and moderators of the blood–brain barrier’s response to systemic inflammation in order to explain the heterogeneity observed in animal and human studies.
The CROONIAN LECTURES on some POINTS CONNECTED with SLEEP, SLEEPLESSNESS, and HYPNOTICS: Delivered before the Royal College of Physicians of London
Authors: J. B. Bradbury
Journal: BMJ (1899)

JuN 24, 1&"# distended, there, were no rose spots, and the spleen could not be felt; there were no herpes.The skin had a diffuse mottling, but no purpuric spots were seen.There was no urethral diselarge.The leucocytes were 23,scdper c.cm., no alteration in a differential count of zoo.The Widal re- action was not present.At io P.m. the temperature had reached xo60, and he was given a bath at 8o0, with ice frictions, which reduced the rectal temperature to 1030.At x P.m. the body seemed to be held much more stiffly.At 2 midnigthe was much worse, and at 2.40 A.M. he died, about three days and three hours from the time of the initial chill.The post-mortem examination (No. 989) showed a diffuse purulent mening- itis of the hemispheres, the base much less involved and the ventricles not'at all affected.Tne cord unfortunately was not examined.There was a recent diffuse nephritis, and the urine in the bladder contained albu- men and tube casts.There was a general pneumococcus infection, no pneumonia or endocarditis, and the pneurnococcus was separated in pure culture from the meningeal exudate.
Abstract 14619: Quality of Life is Associated With Age and Executive Function in Children With Congenital Heart Disease
Authors: Nicole M Hemphill, Christine Voss, Mimi T Kuan, Jimmy Lopez, Ashutosh Sharma, Penny L Sneddon, Kevin C Harris
Journal: Circulation (2019)

Introduction: Children with congenital heart disease (CHD) report lower quality of life (QoL) than healthy children. These patients have increased risk of health complications and cognitive deficit...
235P Efficacy and safety of first-line therapy with fulvestrant or exemestane for postmenopausal ER+/HER2- advanced breast cancer patients after adjuvant nonsteroidal aromatase inhibitor treatment: A randomized, open-label, multicenter study
Authors: J. Wang, B. Xu, L. Cai, Y. Song, L. Kang, T. Sun, Y. Teng, Z. Tong, H. Li, Q. Ouyang, S. Cui, M. Yan, Q. Chen, Y. Yin, Q. Sun, N. Liao, J. Feng, X. Wang
Journal: Annals of Oncology (2021)
Hemoperfusion. Kidney and Liver Support and Detoxification.
Journal: Annals of Internal Medicine (1981)

that the confusion may well be resolved by studying highly purified interferons.All the authors are international experts, the chapters are fully referenced and the book is well produced and edited -though I still think the genitive of interferon should be interferon's.These position papers will be valuable reading for all those who for whatever reason want to understand the present state of the science that lies behind the possible use of interferon in clinical medicinescience that is moving very fast at the moment.
Doctoring doctors
Authors: W. Anderson
Journal: BMJ (1999)

Most people seem to think that doctors get better treatment than everyone else when they are ill, but in my experience doctors and their families often get worse treatment than other patients. I first met this problem when I was a medical student working in anaesthetics. When I arrived at the hospital one morning I found the anaesthetist very upset. A doctor's wife had been admitted 15 minutes before her hysterectomy. Everyone else was admitted the day before so that a proper history could be taken and any necessary preoperative investigations performed. During my career I have come across many other examples.

A newly appointed senior house officer was chatting to a surgeon in the corridor and casually showed him a lesion on her forearm. He advised her to have it removed and put her on the end of the afternoon list. A few days later she was informed brusquely over the telephone that it was a malignant melanoma and would need wide excision and grafting. She was absolutely devastated and, as she was not registered with any general practitioner in the district, ended up talking to a friend of mine for several hours.

A few years ago we discovered that an anaesthetist, a patient of ours, had been treating himself for 10 years for diabetes and hypertension. Both conditions were badly controlled. He said he did not like to admit to other doctors that he was ill.

A surgeon was well known by all his colleagues to have an alcohol problem, but no one did anything about it until he was convicted of drunken driving. He lost his driving licence and was referred to the General Medical Council. He was suspended for 12 months on condition that he accepted treatment.

Another example was the tragic case of a general …
The Hidden Lesion
Authors: Alfred I. Lee, Cassius I. Ochoa Chaar
Journal: New England Journal of Medicine (2016)

A 24-year-old woman presented to the ED with pain in the left leg. She had been training for a 5-km race when, 2 days before presentation, she had crampy pain in her left leg, extending to the left lower abdomen and buttock, plus leg swelling and exertional dyspnea.
Fatty Pancreas Is Independently Associated With Subsequent Diabetes Mellitus Development: A 10-Year Prospective Cohort Study
Authors: Ting Ting Chan, Yee Kit Tse, Rashid Nok-Shun Lui, Grace Lai-Hung Wong, Angel Mei-Ling Chim, Alice Pik-Shan Kong, Jean Woo, David Ka-Wai Yeung, Jill M Abrigo, Winnie Chiu-Wing Chu, Vincent Wai-Sun Wong, Raymond Shing-Yan Tang
Journal: Clinical Gastroenterology and Hepatology (2021)
284P Trastuzumab emtansine (T-DM1) in Asian patients with previously treated HER2-positive locally advanced (LA) or metastatic breast cancer (MBC): Data from the phase III EMILIA study
Authors: S-A. Im, I. Park, J.H. Sohn, Y-H. Im, S.C. Lee, H-K. Chang, H. Macharia, G. Sun, F. Lamour, D-Y. Oh
Journal: Annals of Oncology (2021)
950P Ultra-sensitive and cost-effective method for early stage hepatocellular carcinoma and intrahepatic cholangiocarcinoma detection using plasma cfDNA fragmentomic profiles
Authors: X. Zhang, Z. Wang, X. Wang, W. Tang, R. Liu, H. Bao, X. Chen, S. Wu, X. Wu, Y. Shao, J. Fan, J. Zhou
Journal: Annals of Oncology (2021)
Sixty seconds on . . . sportspeople and jabs
Authors: Gareth Iacobucci
Journal: BMJ (2021)

No, not those kinds of jabs. We’re talking about sports people and covid vaccinations.

It was recently reported1 that fewer than half of the football players at most English Premier League and Football League clubs are vaccinated. As of two weeks ago, the squads of only seven clubs in the Premier League were more than …
1626P The perks of SARS-CoV-2 monitoring through serial nasopharyngeal (NP) swabs in an Italian high prevalence area
Authors: L. Bortot, M. Cinausero, D. Iacono, C. Corvaja, G. Pelizzari, G. Targato, D. Zara, V.J. Andreotti, C. Noto, R. Donato, A. Bin, A.M.M. Minisini, G. Fasola
Journal: Annals of Oncology (2021)
1133P Whole genome sequencing can classify diagnostically challenging tumors
Authors: L.J. Schipper, P. Snaebjornsson, K.G. Samsom, L.J.W. Bosch, F. Lalezari, P. Priestley, C. Shale, N. Jacobs, A.J. van den Broek, P. Roepman, J.J.M. van der Hoeven, N. Steeghs, E. Cuppen, G. Meijer, E.E. Voest, K. Monkhorst
Journal: Annals of Oncology (2021)
LBA4 Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol
Authors: G. Attard, L.C. Brown, N. Clarke, L. Murphy, W. Cross, R. Jones, S. Gillessen, J.M. Russell, A. Cook, J. Bowen, A. Lydon, I.D. Pedley, O. Parikh, S. Chowdhury, Z. Malik, D. Matheson, C. Parker, M.R. Sydes, M.K. Parmar, N.D. James
Journal: Annals of Oncology (2021)
538P Nadunolimab (CAN04), a first-in-class monoclonal antibody against IL1RAP, in combination with chemotherapy in subjects with pancreatic cancer (PDAC) and non-small cell lung cancer (NSCLC)
Authors: A.H. Awada, M. Zematis, S. Ochsenreither, R.L. Eefsen, D. Arnold, S. Cicenas, J. Yachnin, P. Pfeiffer, L. Paz-Ares, C. Jungels, R. Greil, L. Østergaard Poulsen, E. Van Cutsem, I. Garcia Ribas, L. Thorsson, J.J. Collignon
Journal: Annals of Oncology (2021)
927TiP SKYSCRAPER-09: A phase II, randomised, double-blinded study of atezolizumab (Atezo) + tiragolumab (Tira) and atezo + placebo as first-line (1L) therapy for recurrent/metastatic (R/M) PD-L1+ squamous cell carcinoma of the head and neck (SCCHN)
Authors: E. Cohen, J. Fayette, K.J. Harrington, M.L. Johnson, H-F. Kao, S-H. Lee, L.F. Licitra, N. Ngamphaiboon, A. Psyrri, D.J. Wong, M. Afshari, K. Cvijovic, G.R. Goodman, K.M. Komatsubara, C. Matheny, T.Q. Pham, H. Tang, L. Wang, Y. Yan, M. Gillison
Journal: Annals of Oncology (2021)
1775P A novel 89Zr-anti-PD-1 immuno-PET-CT improves response assessment to immunotherapy in lung cancer
Authors: I. Gil Bazo, A. Puyalto, M. Rodriguez-Remirez, I. Lopez, F. Iribarren, M. Torregrosa, M. Ecay, A. Vilalta, M. Collantes
Journal: Annals of Oncology (2021)
Closed-loop neuromodulation in an individual with treatment-resistant depression
Authors: Katherine W. Scangos, Ankit N. Khambhati, Patrick M. Daly, Ghassan S. Makhoul, Leo P. Sugrue, Hashem Zamanian, Tony X. Liu, Vikram R. Rao, Kristin K. Sellers, Heather E. Dawes, Philip A. Starr, Andrew D. Krystal, Edward F. Chang
Journal: Nature Medicine (2021)
1713P Accelerometer measured physical activity (PA) and biomarkers in breast cancer (BC) survivors
Authors: M. Romero-Elias, C. Maximiano, B. Cantos, M. Mendez, M. Mendez, S. Martin, C. Gonzalez, C. Fiuza, H. Cebolla, A. Alvarez-Bustos, M. Blanco, A. Morito, B. Puente, A. Ruiz-Casado
Journal: Annals of Oncology (2021)
HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA
Authors: Eric Leung, Kathy Han, Jinfeng Zou, Zhen Zhao, Yangqiao Zheng, Ting Ting Wang, Ariana Rostami, Lillian L. Siu, Trevor J. Pugh, Scott V. Bratman
Journal: Clinical Cancer Research (2021)

Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings.We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer. HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability.HPV-seq achieved reproducible detection of HPV DNA at levels less than 0.6 copies in cell line data. HPV-seq and dPCR results for patients were highly correlated (R2 = 0.95, P = 1.9 × 10-29) with HPV-seq detecting ctDNA at levels down to 0.03 copies/mL plasma in dPCR-negative posttreatment samples. Detectable HPV ctDNA at end-of-treatment was associated with inferior PFS with 100% sensitivity and 67% specificity for recurrence. Accurate HPV genotyping was successful from 100% of pretreatment samples. HPV ctDNA fragment sizes were consistently shorter than non-cancer-derived cell-free DNA (cfDNA) fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes.HPV-seq is a quantitative method for ctDNA detection that outperforms dPCR and reveals qualitative information about ctDNA. Our findings in this proof-of-principle study could have implications for treatment monitoring of disease burden in HPV-related cancers. Future prospective studies are needed to confirm that patients with undetectable HPV ctDNA following chemoradiotherapy have exceptionally high cure rates.
LBA41 Nivolumab (nivo) ± ipilimumab (ipi) in pre-treated patients with advanced, refractory pulmonary or gastroenteropancreatic poorly differentiated neuroendocrine tumors (NECs) (GCO-001 NIPINEC)
Authors: N. Girard, J. Mazieres, J. Otto, H. Lena, C. Lepage, T. Egenod, D. Smith, J. Madelaine, L. Gérinière, F. El Hajbi, A. Ferru, C. Clément-Duchêne, A. Madroszyk, J. Desrame, F. Morin, A. Langlais, P. Michel, C. Louvet, V. Westeel, T. Walter
Journal: Annals of Oncology (2021)
Primary Tumor Resection and Patients With Asymptomatic Colorectal Cancer and Nonresectable Metastases
Authors: Yuman Fong
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Activation of GM-CSF and TLR2 signaling synergistically enhances antigen-specific antitumor immunity and modulates the tumor microenvironment
Authors: Wan-Lun Yan, Chiao-Chieh Wu, Kuan-Yin Shen, Shih-Jen Liu
Journal: Journal for ImmunoTherapy of Cancer (2021)

The major challenge of antitumor immunotherapy is dealing with the immunosuppressive tumor microenvironment, which involves immature myeloid cell accumulation that results in T cell dysfunction. Myeloid cell activation is induced by Toll-like receptor agonists. Additionally, granulocyte/macrophage colony stimulating factor (GM-CSF) promotes myelopoiesis and recruits myeloid cells. Here, we combined the Toll-like receptor 2 (TLR2) agonist lipoprotein and GM-CSF to assess whether this bifunctional immunotherapy has synergistic effects on myeloid cells and could be further developed as a therapeutic intervention that enhances the antitumor response.We investigated the synergistic effects of biadjuvanted tumor antigen on antigen-presenting cell (APC) activation in bone marrow-derived dendritic cells. Furthermore, therapeutic efficacy was monitored in different tumor models treated via intratumoral or subcutaneous administration routes. The immune effects of the bifunctional fusion protein on myeloid cells in the tumor mass and draining lymph nodes were analyzed by flow cytometry. The induction of cytotoxic T lymphocytes was evaluated via intracellular cytokine levels, perforin/granzyme B staining and an in vivo killing assay.The TLR2 agonist lipoprotein combined with GM-CSF synergistically induced DC maturation, which subsequently enhanced antitumor immunity. In addition, rlipoE7m-MoGM modulated tumor-infiltrating myeloid cell populations. Vaccination with rlipoE7m-MoGM therapy increased the number of CCR7+CD103+ cDC1s, whereas the number of suppressive tumor-associated macrophages was reduced in the tumor lesions. Consistent with this observation, proliferating antigen-specific CD8+ T cells are highly infiltrated within the tumor, and the expression of IFN-r and perforin was most pronounced within antigen-specific CD8+ T cells in mice administered rlipoE7m-MoGM therapy. This finding corresponded with observation that the combination of a TLR2 agonist and GM-CSF provides increased antitumor activity by inhibiting established tumor outgrowth and protecting against metastatic cancer compared with a TLR2 agonist alone. Importantly, tumor growth inhibition was not due to the direct effects of the TLR2 agonist or GM-CSF but was instead due to the induction of antigen-specific immunity.The combination of a TLR2 agonist and GM-CSF has synergistic effects that inhibit tumor growth and modulate tumor-infiltrating APCs. This therapeutic approach could be applied to other tumor antigens to treat different cancers.
Decreasing humoral response among healthcare workers up to 4 months after two doses of BNT162b2 vaccine
Authors: Valentine Marie Ferré, Samuel Lebourgeois, Reyene Menidjel, Gilles Collin, Houssem Redha Chenane, Manuella Onambele Guindi, Yazdan Yazdanpanah, Jean-François Timsit, Charlotte Charpentier, Diane Descamps, Nadhira Fidouh, Benoit Visseaux
Journal: Journal of Infection (2021)
Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
Authors: Elodie Leroux, Romain Perbet, Raphaëlle Caillierez, Kevin Richetin, Sarah Lieger, Jeanne Espourteille, Thomas Bouillet, Séverine Bégard, Clément Danis, Anne Loyens, Nicolas Toni, Nicole Déglon, Vincent Deramecourt, Susanna Schraen-Maschke, Luc Buée, Morvane Colin
Journal: Molecular Therapy (2021)

Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer's disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies.
808P Characteristics and outcomes of women with adenocarcinoma versus squamous cell carcinoma of the vulva: A Japanese Gynecologic Oncology Group study
Authors: S. Nishio, K. Matsuo, S. Matsuzaki, T. Kato, S. Kamiura, H. Adachi, M. Okadome, T. Nakamura, M. Mikami, T. Enomoto
Journal: Annals of Oncology (2021)