tbuckley/cabot-search huggingface dataset:
Photoacoustic and magnetic resonance imaging-based gene and photothermal therapy using mesoporous nanoagents
Authors: Hao Huang, Guotao Yuan, Ying Xu, Yuan Gao, Qiulian Mao, Yin Zhang, Lu Bai, Weijie Li, Anqing Wu, Wentao Hu, Yue Pan, Guangming Zhou
Journal: Bioactive Materials (2021)

The integration of photothermal therapy (PTT) with gene therapy (GT) in a single nanoscale platform demonstrates great potential in cancer therapy. Porous iron oxide nanoagents (PIONs) are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy. However, the therapeutic efficacy of PIONs-mediated GT has not been studied. The long noncoding RNA (lncRNA) CRYBG3 (LNC CRYBG3), a lncRNA induced by heavy ion irradiation in lung cancer cells, has been reported to directly bind to globular actin (G-actin) and cause degradation of cytoskeleton and blocking of cytokinesis, thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug. In the present study, we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. The combination therapy showed a high cancer cell killing efficacy, and the cure rate was better than that achieved using PTT or GT alone. Moreover, as a type of magnetic nanoagent, PIONs can be used for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) both in vitro and in vivo. These findings indicate that the new combination therapy has high potential for cancer treatment.
COVID-19 in patients with CLL: improved survival outcomes and update on management strategies
Authors: Lindsey E. Roeker, Toby A. Eyre, Meghan C. Thompson, Nicole Lamanna, Alexander R. Coltoff, Matthew S. Davids, Peter O. Baker, Lori Leslie, Kerry A. Rogers, John N. Allan, Raul Cordoba, Alberto Lopez-Garcia, Darko Antic, John M. Pagel, Nicolas Martinez-Calle, José Antonio García-Marco, Jose-Ángel Hernández-Rivas, Fatima Miras, Catherine C. Coombs, Anders Österborg, Lotta Hansson, Amanda N. Seddon, Javier López Jiménez, Matthew R. Wilson, Dima El-Sharkawi, Daniel Wojenski, Shuo Ma, Talha Munir, Susana Valenciano, Erlene Seymour, Paul M. Barr, Jeffrey Pu, Piers E. M. Patten, Guilherme F. Perini, Scott F. Huntington, Helen Parry, Suchitra Sundaram, Alan Skarbnik, Manali Kamdar, Ryan Jacobs, Harriet Walter, Renata Walewska, Angus Broom, Sonia Lebowitz, Krista M. Isaac, Craig A. Portell, Inhye E. Ahn, Chaitra S. Ujjani, Mazyar Shadman, Sigrid S. Skånland, Elise A. Chong, Anthony R. Mato
Journal: Blood (2021)
P44-9 A case of recurrent gastric cancer with drug-induced immune thrombocytopenia caused by trastuzumab
Authors: Yuko Takano, Satoshi Furune, Sachi Morita, Megumi Inoue, Tomoya Shimokata, Mihoko Sugishita, Ayako Mitsuma, Maeda Osamu, Yuichi Ando
Journal: Annals of Oncology (2021)
Insights on Neural Response to Racist Threats
Authors: Robert O. Motley, Cynthia Rogers
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Art in Endoscopy: Tunnel “delivery” of a large esophageal leiomyoma
Authors: Shaimaa Elkholy, Kareem Essam, Khaled Ragab, Dalia Abd El-Kareem, Mohamed El-Sherbiny
Journal: Endoscopy (2021)

A 42-year-old man complaining of dysphagia was diagnosed as having an esophageal leiomyoma, about 3.3 × 1.7 cm in size and originating from the muscularis propria (4th layer). Submucosal tunneling endoscopic resection (STER) was the optimal option for the patient. A submucosal bleb was created 5 cm proximal to the lesion and the tunnel opening was incised. This was followed by dissection on either side of the lesion and dissection through the muscle, until the lesion was totally separated and “delivered” through the tunnel. The opening was then closed with endoclips.
P-27 The efficacy and safety of XELOX/SOX plus bevacizumab as neoadjuvant chemotherapy for locally advanced rectal cancer compared with XELOX/SOX: A retrospective study
Authors: N. Sakaguchi, T. Terazawa, Y. Ishizuka, H. Kodama, T. Miyamoto, F. Shimamoto, M. Goto, K. Izuhara, H. Hamamoto, W. Osumi, M. Yamamoto, K. Tanaka, J. Okuda, K. Uchiyama, K. Higuchi
Journal: Annals of Oncology (2021)
Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination
Authors: Tina Schmidt, Verena Klemis, David Schub, Janine Mihm, Franziska Hielscher, Stefanie Marx, Amina Abu-Omar, Laura Ziegler, Candida Guckelmus, Rebecca Urschel, Sophie Schneitler, Sören L. Becker, Barbara C. Gärtner, Urban Sester, Martina Sester
Journal: Nature Medicine (2021)

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
Global Incidence and Mortality of Gastric Cancer, 1980-2018
Authors: Martin C. S. Wong, Junjie Huang, Paul S. F. Chan, Peter Choi, Xiang Qian Lao, Shannon Melissa Chan, Anthony Teoh, Peter Liang
Journal: JAMA Network Open (2021)

Gastric cancer is one of the most common cancers, with a high mortality-to-incidence ratio. It is uncertain whether developed nations may encounter an increasing burden of gastric cancer in young adults, as occurs for other cancers.To evaluate the incidence and mortality of gastric cancer and compare the global incidence trends between younger (<40 years) and older (≥40 years) populations.This population-based cohort study analyzed data from global and national cancer registries, including data from 1980 to 2018, with at least 15 calendar years of incidence and mortality data. Data on age-standardized incidence and mortality rates of gastric cancer among 48 countries were retrieved from the Surveillance, Epidemiology, and End Results Program, the National Cancer Institute, the Nordic Cancer Registries, and the World Health Organization Mortality Database. The 10-year incidence trend of gastric cancer was assessed by age and sex. The 2018 GLOBOCAN database was used for reporting the global incidence and mortality of gastric cancer, the most recent data available at the time of analysis. Analyses were performed between January 10, 2020, and March 20, 2020.The average annual percent change (AAPC) of the incidence and mortality trends as evaluated by joinpoint regression analysis.A total of 1 033 701 new cases of gastric cancer and 782 685 related deaths were reported in 2018. Overall, the incidence of gastric cancer decreased in 29 countries, and mortality decreased in 41 countries. The age-standardized incidence of gastric cancer decreased from a range of 2.6 to 59.1 in 1980 to a range of 2.5 to 56.8 in 2018 per 100 000 persons. The overall age-standardized mortality rate changed from a range of 1.3 to 25.8 in 1980 to a range of 1.5 to 18.5 in 2018 per 100 000 persons, but increasing mortality was observed in Thailand (female: AAPC, 5.30; 95% CI, 4.38-6.23; P < .001; male: AAPC, 3.92; 95% CI, 2.14-5.74; P < .001). The incidence of gastric cancer decreased in most regions among individuals 40 years or older and increased in populations younger than 40 years in several countries, including Sweden (male: AAPC, 13.92; 95% CI, 7.16-21.11; P = .001), Ecuador (female: AAPC, 6.05; 95% CI, 1.40-10.92; P = .02), and the UK (male: AAPC, 4.27; 95% CI, 0.15-8.55; P = .04; female: AAPC, 3.60; 95% CI, 3.59-3.61; P < .001).In this population-based cohort study, an increasing incidence of gastric cancer was observed in younger individuals in some countries, highlighting the need for more preventive strategies in younger populations. Future research should explore the reasons for these epidemiologic trends.
Vijayapura C Devakumar
Authors: Vinodh Devakumar
Journal: BMJ (2021)

Vijayapura C Devakumar (“Vijay”) came to England to start his NHS career in November 1966. He undertook a number of junior doctor training posts across the UK and successfully completed his MRCPsych qualification. After registrar and senior registrar posts, he was appointed as consultant psychiatrist at Burnley and Rossendale Hospitals in Lancashire in 1978. He …
THE FACTORS CONCERNED IN THE APPEARANCE OF NUCLEATED RED BLOOD CORPUSCLES IN THE PERIPHERAL BLOOD
Authors: Cecil K. Drinker, Katherine R. Drinker, Henry A. Kreutzmann
Journal: The Journal of Experimental Medicine (1918)

1. Increase in circulatory rate caused by hard exercise has no power to dislocate nucleated red cells from the bone marrow either in normal, in anemic, in hyperplastic, or in anemic and hyperplastic animals. 2. In anemic and hyperplastic animals pseudocrises of nucleated red cells can be produced at certain periods by hard exercise, but careful analysis leads inevitably to the conclusion that the increase in these cells is merely a more accurate expression of circulatory content at the time of the procedure. 3. Section of the vasomotor nerves to the four limbs with consequent dilatation of the marrow vessels and increased blood flow through the tissue does not result in the freeing of nucleated red cells from the bone marrow.
Real-world data for endoscopic therapy in LGD: not looking so good
Authors: Sachin Srinivasan, Prateek Sharma
Journal: Gut (2021)

Low-grade dysplasia (LGD) in Barrett’s oesophagus (BE),1 due to the inconsistency in its diagnosis, identification and cancer progression, has been a management challenge for gastroenterologists. LGD, as classified by the Vienna classification, includes a histological subtype of BE where nuclei are hyperchromatic, enlarged and stratified, with this change extending to the surface epithelial cells and loss of surface maturation.2 However, there is a coexistent inflammation-mediated epithelial injury that can make the histopathological diagnosis difficult. There is significant variability in the histopathological diagnosis and progression rates of LGD. A recent, large, multicentre study involving pathologists from the USA and Europe demonstrated that the interobserver agreement (IOA) for the diagnosis of LGD is very poor (![Formula][1]</img>).3 Similarly, several other studies have shown IOAs ranging from 0.17 to 0.32.4 5 Similarly, there is also a wide range in progression rates (0.02%6– 11.4%4) from LGD to neoplasia, and other studies also report either regression or persistence of LGD without neoplastic progression. A recent study also demonstrated that BE referral centres identified high grade dysplasia/esophageal adenocarcinoma (HGD/EAC) in 27% of the patients referred with a recent diagnosis of LGD, suggesting overestimation of neoplastic progression.7 Thus, the current expert best practice recommendation is to have an expert gastrointestinal pathologist confirm the diagnosis of LGD,8–10 repeat examination with white-light endoscopy (consideration for virtual chromoendoscopy) within 3–6 months of confirmed LGD to rule out higher grade lesions, that is, coexisting high-grade dysplasia or cancer8 and consideration for either … [1]: /embed/mml-math-1.gif
Infigratinib: First Approval
Authors: Connie Kang
Journal: Drugs (2021)

Infigratinib (TRUSELTIQTM), a fibroblast growth factor receptor (FGFR)-specific tyrosine kinase inhibitor, is being co-developed by QED Therapeutics and Helsinn for the treatment of cholangiocarcinoma, urothelial carcinoma and other FGFR-driven conditions. Infigratinib was recently approved in the USA for the treatment of previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by a test approved by the US Food and Drug Administration. This article summarizes the milestones in the development of infigratinib leading to this first approval for advanced cholangiocarcinoma.
P-159 HERIZON: Phase 2 part of the IMU-131 HER2/neu vaccine plus chemotherapy study randomized in patients with HER2/NEU overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction
Authors: M. Maglakelidze, D. Ryspayenva, I. Bulat, Z. Andric, I. Nikolic, T. Chawla, V. Choudhary, G. Venkata, D. Radosavljevic, Z. Petrovic, U. Wiedermann, L. Chong, R. Laeufle, N. Ede, B. Nixon, A. Good
Journal: Annals of Oncology (2021)
Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease
Authors: Alice Tang, Ana Nicolle Strat, Mahmudur Rahman, Helen Zhang, Weili Bao, Yunfeng Liu, David Shi, Xiuli An, Deepa Manwani, Patricia Shi, Karina Yazdanbakhsh, Avital Mendelson
Journal: Blood (2021)

Abstract Sickle cell disease (SCD) is characterized by hemolytic anemia, which can trigger oxidative stress, inflammation, and tissue injury that contribute to disease complications. Bone marrow mesenchymal stromal cells (MSCs) tightly regulate hematopoietic stem cell (HSC) homeostasis in health and disease, but their functionality in SCD remains unclear. We identified for the first time that murine SCD MSCs have altered gene signatures, reduced stem cell properties, and increased oxidative stress, due in part to hemolysis. Murine SCD MSCs had lower HSC maintenance ability in vitro and in vivo, as manifested by increased HSC mobilization and decreased HSC engraftment after transplant. Activation of Toll-like receptor-4 through p65 in MSCs further contributed to MSC dysfunction. Transfusions led to an improved MSC and HSC oxidative state in SCD mice. Improving the regulation between MSCs and HSCs has vital implications for enhancing clinical HSC transplantation and gene therapy outcomes and for identification of new molecular targets for alleviating SCD complications.
P-15 Diagnostic potential of erythrocyte and serum fatty acids in spotting adenomatous polyps and identifying the early stages of colorectal cancer depending on tumor localization
Authors: M. Kruchinina, A. Gromov, V. Kruchinin, M. Shashkov, A. Sokolova, I. Yakovina, A. Shestov
Journal: Annals of Oncology (2021)
P-95 EV-202: An open-label, multicenter, phase 2 study of enfortumab vedotin in patients with previously treated locally advanced or metastatic solid tumors, including upper gastrointestinal cancers
Authors: K. Muro, J. Bruce, J. Baranda, S. Gorla, C. Wu, F. Braiteh
Journal: Annals of Oncology (2021)
Frequent LPA KIV-2 Variants Lower Lipoprotein(a) Concentrations and Protect Against Coronary Artery Disease
Authors: Johanna F. Schachtl-Riess, Azin Kheirkhah, Rebecca Grüneis, Silvia Di Maio, Sebastian Schoenherr, Gertraud Streiter, Jamie Lee Losso, Bernhard Paulweber, Kai-Uwe Eckardt, Anna Köttgen, Claudia Lamina, Florian Kronenberg, Stefan Coassin, Kai-Uwe Eckardt, Heike Meiselbach, Markus P. Schneider, Mario Schiffer, Hans-Ulrich Prokosch, Barbara Bärthlein, Andreas Beck, André Reis, Arif B. Ekici, Susanne Becker, Dinah Becker-Grosspitsch, Ulrike Alberth-Schmidt, Birgit Hausknecht, Anke Weigel, Gerd Walz, Anna Köttgen, Ulla T. Schultheiß, Fruzsina Kotsis, Simone Meder, Erna Mitsch, Ursula Reinhard, Jürgen Floege, Turgay Saritas, Elke Schaeffner, Seema Baid-Agrawal, Kerstin Theisen, Hermann Haller, Jan Menne, Martin Zeier, Claudia Sommerer, Johanna Theilinger, Gunter Wolf, Martin Busch, Rainer Paul, Thomas Sitter, Christoph Wanner, Vera Krane, Antje Börner-Klein, Britta Bauer, Florian Kronenberg, Julia Raschenberger, Barbara Kollerits, Lukas Forer, Sebastian Schönherr, Hansi Weissensteiner, Peter Oefner, Wolfram Gronwald, Matthias Schmid, Jennifer Nadal
Journal: Journal of the American College of Cardiology (2021)

Lipoprotein(a) (Lp(a)) concentrations are a major independent risk factor for coronary artery disease (CAD) and are mainly determined by variation in LPA. Up to 70% of the LPA coding sequence is located in the hypervariable kringle IV type 2 (KIV-2) region. It is hardly accessible by conventional technologies, but may contain functional variants. This study sought to investigate the new, very frequent splicing variant KIV-2 4733G>A on Lp(a) and CAD. We genotyped 4733G>A in the GCKD (German Chronic Kidney Disease) study (n = 4,673) by allele-specific polymerase chain reaction, performed minigene assays, identified proxy single nucleotide polymorphisms and used them to characterize its effect on CAD by survival analysis in UK Biobank (n = 440,234). Frequencies in ethnic groups were assessed in the 1000 Genomes Project. The 4733G>A variant (38.2% carrier frequency) was found in most isoform sizes. It reduces allelic expression without abolishing protein production, lowers Lp(a) by 13.6 mg/dL (95% CI: 12.5-14.7; P < 0.0001) and is the strongest variance-explaining factor after the smaller isoform. Splicing of minigenes was modified. Compound heterozygosity (4.6% of the population) for 4733G>A and 4925G>A, another KIV-2 splicing mutation, reduces Lp(a) by 31.8 mg/dL and most importantly narrows the interquartile range by 9-fold (from 42.1 to 4.6 mg/dL) when compared to the wild type. In UK Biobank 4733G>A alone and compound heterozygosity with 4925G>A reduced HR for CAD by 9% (95% CI: 7%-11%) and 12% (95% CI: 7%-16%) (both P < 0.001). Frequencies in ethnicities differ notably. Functional variants in the previously inaccessible LPA KIV-2 region cooperate in determining Lp(a) variance and CAD risk. Even a moderate but lifelong genetic Lp(a) reduction translates to a noticeable CAD risk reduction.
Antihypertensive Agents
Authors: Edward D. Freis
Journal: New England Journal of Medicine (1962)

SINCE the average life expectancy of hypertensive patients is less than that of the general population1 2 3 4 5 the question arises whether it is advisable to lower the blood pressure by means of antihypertensive agents in all patients with this disease. The arguments in favor of this approach are based on a number of clinical and experimental observations.Arguments for TreatmentThe mortality in hypertension arises from the complications produced by accelerated atherosclerosis, arteriolosclerosis or necrosis and myocardial hypertrophy and dilatation. It has been demonstrated that the elevated blood pressure is the important factor in producing arteriolar lesions in hypertensive rats.6 7 8 Furthermore, . . .
Letter to the editor: radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers
Authors: Mateus Trinconi Cunha, Vinicius Jardim Carvalho, Rafael Maffei Loureiro, Carlos Eduardo Brantis-de-Carvalho, Murilo Bicudo Cintra, Gilberto de Castro Junior
Journal: Journal for ImmunoTherapy of Cancer (2021)

A commentary on the original research article: ‘Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers’. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.
Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post–Cardiac Arrest
Authors: Ryan L. Hoiland, Philip N. Ainslie, Cheryl L. Wellington, Jennifer Cooper, Sophie Stukas, Sonny Thiara, Denise Foster, Nicholas A. Fergusson, Edward M. Conway, David K. Menon, Peter Gooderham, Veronica Hirsch-Reinshagen, Donald E. Griesdale, Mypinder S. Sekhon
Journal: Circulation Research (2021)

Rationale: Secondary brain hypoxia portends significant mortality in ischemic brain diseases; yet, our understanding of hypoxic ischemic brain injury (HIBI) pathophysiology in humans remains rudimentary. Objective: To quantify the impact of secondary brain hypoxia on injury to the neurovascular unit in patients with HIBI. Methods and Results: We conducted a prospective interventional study of invasive neuromonitoring in 18 post–cardiac arrest patients with HIBI. The partial pressures of brain tissue O 2 (PbtO 2 ) and intracranial pressure were directly measured via intraparenchymal microcatheters. To isolate the cerebrovascular bed, we conducted paired sampling of arterial and jugular venous bulb blood and calculated the transcerebral release of biomarkers of neurovascular injury and inflammation in the patients with HIBI and 14 healthy volunteers for control comparisons. Ten patients with HIBI exhibited secondary brain hypoxia (PbtO 2 &lt;20 mmHg), while 8 exhibited brain normoxia (PbtO 2 ≥20 mmHg). In the patients with secondary brain hypoxia, we observed active cerebral release of glial fibrillary acidic protein (−161 [−3695 to −75] pg/mL; P =0.0078), neurofilament light chain (−231 [−370 to −11] pg/mL; P =0.010), total tau (−32 [−310 to −3] pg/mL; P =0.0039), neuron-specific enolase (−14 890 [−148 813 to −3311] pg/mL; P =0.0039), and ubiquitin carboxy-terminal hydrolase L1 (−14.7 [−37.7 to −4.1] pg/mL; P =0.0059) indicating de novo neuroglial injury. This injury was unrelated to the systemic global ischemic burden or cerebral endothelial injury but rather was associated with cerebral release of IL-6 (interleukin-6; −10.3 [−43.0 to −4.2] pg/mL; P =0.0039). No cerebral release of the aforementioned biomarkers was observed in patients with HIBI with brain normoxia or the healthy volunteers. Hyperosmolar therapy in the patients with secondary brain hypoxia reduced the partial pressure of jugular venous O 2 -to-PbtO 2 gradient (39.6 [34.1–51.1] versus 32.0 [24.5–39.2] mm Hg; P =0.0078) and increased PbtO 2 (17.0 [9.1–19.7] versus 20.2 [11.9–22.7] mm Hg; P =0.039) suggesting improved cerebrovascular-to-parenchymal O 2 transport. Conclusions: Secondary brain hypoxia is associated with de novo neuroglial injury and cerebral release of IL-6. Mitigating cerebrovascular-to-parenchymal limitations to O 2 transport is a promising therapeutic strategy for patients with HIBI with secondary brain hypoxia. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03609333.