tbuckley/cabot-search huggingface dataset:
CSF-1R inhibitor, pexidartinib, sensitizes esophageal cancer to PD-1 immune checkpoint blockade in a rat model.
Authors: Michael Paskewicz, Ashten Omstead, Ping Zheng, Anastasia Gorbunova, Madison Salvitti, Adam Alleyne, Payton Reed, Sydne Ballengee, Nabeela Islam, Blair A. Jobe, Ronan Joseph Kelly, Ali Hussainy Zaidi
Journal: Journal of Clinical Oncology (2022)

333 Background: Esophageal adenocarcinoma (EAC) is a leading cause of cancer deaths. Pexidartinib, is a multi-gene tyrosine kinase inhibitor, targeting FLT3, KIT and CSF1R. In particular, pexidartinib by targeting CSF-1R down modulates macrophage mediated pro-survival tumor signaling. Recently, CSF-1R inhibitors have successfully shown to enhance antitumor activity of PD-1/PD-L1 inhibitors by suppressing tumor immune evasion, in multiple solid tumors. Methods: Seventy-two rats underwent an end-to-side esophagojejunostomy to induce gastroesophageal reflux, resulting in EAC carcinogenesis. At 32 weeks postoperatively, tumor bearing animals were randomized to a dose of 30mg/kg of pexidartinib or vehicle control, 5 days on and 2 days off (14 day cycle), for a total of 3 cycles. A PD-1 inhibitor, AUNP-12, at a dose of 3mg/kg or placebo, was administered on day 12 of each cycle. At 38 weeks postoperatively animals were euthanized. Safety and efficacy was evaluated by objective health assessments, pre and posttreatment MRI, RT-PCR, immunofluorescent labeling and a serum cytokine assay. Results: The pexidartinib +/- PD-1 inhibitor (Px+P and Px-P) groups demonstrated no significant difference in daily weight change (p = 0.98) or in mortality (p = 0.59) when compared to vehicle control (V+P and V-P) groups. On post-mortem serum analysis AST (p = 0.01) and ALT (p = 0.001) were elevated, while albumin (p = 0.57) and BUN/creatinine ratio (p = 0.09) were reported within normal ranges, when comparing treatment to placebo groups. Pre to posttreatment, mean MRI tumor volume decreased by 37% and 54% in the Px-P and Px+P animals and increased by 147% and 88% in the V+P and V-P animals, respectively (p = &lt; 0.0001). Overall response rate was 69% and 87% in Px-P and Px+P animals compared to 21% and 13% in V-P and V+P animals, respectively (p = &lt; 0.0001). Downstream gene expression demonstrated upregulation of TNF-α (p = 0.003), IFN-γ (p = 0.002) and IL-6 (p = 0.0001) and downregulation of IL-13 (p = 0.051), IL-10 (p = 0.051), TGF-β (p = 0.024) and Arg-1 (p = 0.0003), in treatment vs. placebo animals. Increased apoptosis (Cas-3 p = 0.0005) and reduced proliferation (Ki-67 p = &lt; 0.0001) were reported in the treatment animals. Higher CD3 + CD8 + T cell densities and CD86/CD206 macrophage ratio was reported in treatment groups compared to placebo (p = &lt; 0.0001). Serum cytokine levels significantly displayed upregulation of TNF-α and IFN-γ and downregulation of IL-4 and IL-10 in the treatment animals compared to the placebo. Conclusions: Overall, this study established a promising combinatorial strategy using a CSF-1R inhibitor to overcome resistance to PD-1/PD-L1 axis blockade in an esophageal cancer model, providing the rationale for future clinical strategies.
This Week in JAMA
Journal: JAMA (2011)

A Piece of My Mind"While I believe that media campaigns, advocacy groups, and physicians have systematically exaggerated the benefits of cancer screening and have downplayedor, worse, ignored-its harms, I also believe that both benefits and harms exist."From "Making the Call." SEE PAGE 2649 Medical News & PerspectivesMedical experts at the NIH's Undiagnosed Diseases Program are combining genomics with traditional clinical evaluation to offer answers to patients with baffling conditions.
Highlights from the Literature
Journal: Neuro-Oncology (2021)

Journal Article Highlights from the Literature Get access Neuro-Oncology, Volume 23, Issue 12, December 2021, Pages 2000–2003, https://doi.org/10.1093/neuonc/noab254 Published: 08 November 2021 Article history Corrected and typeset: 08 November 2021 Published: 08 November 2021
A population‐based study of 92 clinically recognized risk factors for heart failure: co‐occurrence, prognosis and preventive potential
Authors: Amitava Banerjee, Laura Pasea, Sheng‐Chia Chung, Kenan Direk, Folkert W. Asselbergs, Diederick E. Grobbee, Dipak Kotecha, Stefan D. Anker, Tomasz Dyszynski, Benoît Tyl, Spiros Denaxas, R. Thomas Lumbers, Harry Hemingway
Journal: European Journal of Heart Failure (2021)

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.
Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects
Authors: Laëtitia Kermasson, Dmitri Churikov, Aya Awad, Riham Smoom, Elodie Lainey, Fabien Touzot, Séverine Audebert-Bellanger, Sophie Haro, Lauréline Roger, Emilia Costa, Maload Mouf, Adriana Bottero, Matias Oleastro, Chrystelle Abdo, Jean-Pierre de Villartay, Vincent Géli, Yehuda Tzfati, Isabelle Callebaut, Silvia Danielian, Gabriela Soares, Caroline Kannengiesser, Patrick Revy
Journal: Blood (2022)

Inherited bone marrow failure syndromes (IBMFSs) are a group of disorders typified by impaired production of 1 or several blood cell types. The telomere biology disorders dyskeratosis congenita (DC) and its severe variant, Høyeraal-Hreidarsson (HH) syndrome, are rare IBMFSs characterized by bone marrow failure, developmental defects, and various premature aging complications associated with critically short telomeres. We identified biallelic variants in the gene encoding the 5'-to-3' DNA exonuclease Apollo/SNM1B in 3 unrelated patients presenting with a DC/HH phenotype consisting of early-onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly, and/or intrauterine growth retardation. All 3 patients carry a homozygous or compound heterozygous (in combination with a null allele) missense variant affecting the same residue L142 (L142F or L142S) located in the catalytic domain of Apollo. Apollo-deficient cells from patients exhibited spontaneous chromosome instability and impaired DNA repair that was complemented by CRISPR/Cas9-mediated gene correction. Furthermore, patients' cells showed signs of telomere fragility that were not associated with global reduction of telomere length. Unlike patients' cells, human Apollo KO HT1080 cell lines showed strong telomere dysfunction accompanied by excessive telomere shortening, suggesting that the L142S and L142F Apollo variants are hypomorphic. Collectively, these findings define human Apollo as a genome caretaker and identify biallelic Apollo variants as a genetic cause of a hitherto unrecognized severe IBMFS that combines clinical hallmarks of DC/HH with normal telomere length.
Anterior mediastinal lesion
Authors: J. C. Reed
Journal: JAMA (1977)

A LESION anterior to a curved vertical line extending along the posterior border of the heart and anterior margin of the trachea is considered to lie in the anterior mediastinum.<sup>1</sup> <h3>Common</h3> Aneurysm of ascending aorta or sinus of Valsalva; buckled innominate artery Lymphoma (especially nodular sclerosing Hodgkin) Morgagni hernia, hepatic herniation Pericardial cyst Retrosternal thyroid Teratoid lesion (benign or malignant teratoma, dermoid cyst,* seminoma, choriocarcinoma, embryonal cell carcinoma) Thymic lesion (benign or malignant thymoma,* thymic cyst,* thymolipoma, lymphoma arising in thymus, thymic hyperplasia ) <h3>Uncommon</h3> Anomalous left superior vena cava Bronchogenic cyst Cardiac tumor or aneurysm Chemodectoma Cystic hygroma, lymphangioma Hematoma Lymphoid hyperplasia, benign Mediastinitis, mediastinal abscess or fibrosis Mesenchymal tumor Neurofibroma Pericardial tumor Superior vena caval dilation Items distinguished by an asterisk can calcify . <h3>Diagnosis</h3> Benign thymoma. <h3>Comment</h3> In the
A randomized controlled phase III trial comparing two chemotherapy regimen and chemoradiotherapy regimen as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study.
Authors: Ken Kato, Yoshinori Ito, Hiroyuki Daiko, Soji Ozawa, Takashi Ogata, Hiroki Hara, Takashi Kojima, Tetsuya Abe, Takeo Bamba, Masaya Watanabe, Hirofumi Kawakubo, Yuichi Shibuya, Yasuhiro Tsubosa, Naoki Takegawa, Takeshi Kajiwara, Hideo Baba, Masaki Ueno, Ryunosuke Machida, Kenichi Nakamura, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2022)

238 Background: Neoadjuvant treatment is the standard care for locally advanced esophageal squamous cell cancer (ESCC). JCOG1109 (UMIN000009482) compared the doublet and triplet of chemotherapy and chemoradiotherapy as neoadjuvant treatment. Methods: Eligible patients (pts) with ESCC of clinical stage IB, II, III (excluding T4) (UICC 7th) from 44 institutions were randomized 1:1:1 to neoadjuvant CF (cisplatin 80 mg/m 2 on day1 plus 5-FU 800 mg/m 2 on days 1-5 Q3W/2course), DCF (docetaxel 70 mg/m 2 on day 1, cisplatin 70 mg/m 2 on day1, plus 5-FU 750 mg/m 2 on days 1-5 Q3W/3 course), or CF-RT (cisplatin 75 mg/m 2 on day 1 plus 5-FU 1000 mg/m 2 on days 1-4 Q4W/2course, radiation 41.4 Gy/23 fr). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), %R0 resection, %objective response by neoadjuvant therapy, %pathological complete response (pCR) and safety. Differences in OS was assessed in the ITT using the stratified log-rank test. The data cutoff date for the analysis was July 20, 2021. Results: Of 601 pts 199 CF, 202 DCF, and 200 CF-RT were enrolled from December 5, 2012 to July 20, 2018, respectively. Among 601 pts, 88.2% were male, median (range) age was 65 (30-75), clinical stage III (nonT4) pts were 62.6%. Median follow-up time (range) was 4.2 years (y) (0-8.5). Median OS in CF, DCF, and CF-RT arm were 4.6 y, not reached (NR), and 6.0y, and 3-year OS was 62.6%, 72.1%, and 68.3%, respectively (stratified log-rank test: p = 0.006 for CF vs. DCF and p = 0.12 for CF vs. CF-RT). By stratified Cox regression analysis for OS, hazard ratios (HR) [95% CI] was 0.68 [0.50–0.92] for CF vs. DCF and 0.84 [0.63–1.12] for CF vs. CF-RT. Median PFS in CF, DCF, and CF-RT arm were 2.7 y, NR, and 5.3 y, and 3-year PFS was 47.7%, 61.8%, and 58.5%, respectively. R0 resection was achieved in 168 (84.4%), 173 (85.6%), and 175 (87.5%), and pCR was 4 (2.1%), 40 (19.8%), and 77 (38.5%), respectively. During neoadjuvant therapy, febrile neutropenia in CF, DCF, and CF-RT arm were 1.0%, 16.3% and 4.7%, and esophagitis (grade&gt;3) were 1.0%, 1.0% and 8.9%, respectively. The treatment-related death was seen in 3 (1.5%), 4 (2.0%), and 2 (1.0%), in CF, DCF, and CF-RT arm, respectively. Conclusions: DCF significantly improved OS over CF as neoadjuvant therapy for locally advanced ESCC, with a manageable toxicity profile. DCF represents a new standard neoadjuvant treatment for ESCC. Clinical trial information: UMIN000009482.
Physician Health Care Visits for Mental Health and Substance Use During the COVID-19 Pandemic in Ontario, Canada
Authors: Daniel T. Myran, Nathan Cantor, Emily Rhodes, Michael Pugliese, Jennifer Hensel, Monica Taljaard, Robert Talarico, Amit X. Garg, Eric McArthur, Cheng-Wei Liu, Nivethika Jeyakumar, Christopher Simon, Taylor McFadden, Caroline Gerin-Lajoie, Manish M. Sood, Peter Tanuseputro
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Physicians self-report high levels of symptoms of anxiety and depression, and surveys suggest these symptoms have been exacerbated by the COVID-19 pandemic. However, it is not known whether pandemic-related stressors have led to increases in health care visits related to mental health or substance use among physicians. <h3>Objective</h3> To evaluate the association between the COVID-19 pandemic and changes in outpatient health care visits by physicians related to mental health and substance use and explore differences across physician subgroups of interest. <h3>Design, Setting, and Participants</h3> A population-based cohort study was conducted using health administrative data collected from the universal health system (Ontario Health Insurance Plan) of Ontario, Canada, from March 1, 2017, to March 10, 2021. Participants included 34 055 physicians, residents, and fellows who registered with the College of Physicians and Surgeons of Ontario between 1990 and 2018 and were eligible for the Ontario Health Insurance Plan during the study period. Autoregressive integrated moving average models and generalized estimating equations were used in analyses. <h3>Exposures</h3> The period during the COVID-19 pandemic (March 11, 2020, to March 10, 2021) compared with the period before the pandemic. <h3>Main Outcomes and Measures</h3> The primary outcome was in-person, telemedicine, and virtual care outpatient visits to a psychiatrist or family medicine and general practice clinicians related to mental health and substance use. <h3>Results</h3> In the 34 055 practicing physicians (mean [SD] age, 41.7 [10.0] years, 17 918 [52.6%] male), the annual crude number of visits per 1000 physicians increased by 27%, from 816.8 before the COVID-19 pandemic to 1037.5 during the pandemic (adjusted incident rate ratio per physician, 1.13; 95% CI, 1.07-1.19). The absolute proportion of physicians with 1 or more mental health and substance use visits within a year increased from 12.3% before to 13.4% during the pandemic (adjusted odds ratio, 1.08; 95% CI, 1.03-1.14). The relative increase was significantly greater in physicians without a prior mental health and substance use history (adjusted incident rate ratio, 1.72; 95% CI, 1.60-1.85) than in physicians with a prior mental health and substance use history. <h3>Conclusions and Relevance</h3> In this study, the COVID-19 pandemic was associated with a substantial increase in mental health and substance use visits among physicians. Physician mental health may have worsened during the pandemic, highlighting a potential greater requirement for access to mental health services and system level change.
PRIVILEGE DOES NOT EXTEND TO CRIMINAL CASES.
Journal: JAMA (1894)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
DENTAL SEPSIS
Authors: J. G. Turner
Journal: BMJ (1914)

JOURNLDENTAL SEPSIS. [JUNE 6, 19I4 other parts of the book, notably in the clhapter on lhydro- neplirosis, which is the best of the chapters that deal with the kiidney.There is little that is original, and the author lhas drawnl largely on the wealth of German and French irological literature.He appears to have little acquaint- ance wvith modern English practice.For instance, if he were to use the aero-urethroscope invented by Hurry Fenwick and perfected by Wyndham Powell, lhe would not describe ulcerations and erosions of the urethra.Tlhese ulcerations are never seen with the a6ro-urethroscope, wlichl, being passed down under air distension, under control of the eye, does no damage to tlle uretlhral mucosa.The clhapters on gonorrhoea are a little disappointing, as they are veiy, prolix on thepry and not sufficiently clear on details of treatment, and it is not of practical assistance to discuss prostatitis in a separate clhapter under the lheading of diseases of the prostate, wlhen it is.part and parcel of most cases cf gonorrlloea.We are glad to read a book whllich is an earnest advocate of local treatment from the very onset of acute gonorrhoea; but we are surprised to read that the author has obtained better results With injections than with Janet's irrigations.The cllapter on serum and-vaccine therapy is excellent in tlleory, but here again it is disappointinug in practice, as none of the author's own detailed results in this line of treatment anr given,and wee slhould be surprised to learn that they are as roseate as the remarks on theory would lead us to believe.A good feature of tlle book is the excellence of the -illustrations; those illustrating.operative surgery are very clear and useful, and Plate III, a coloured plate of conditions seen by the cystoscope, is a masterpiece.NOTES ON-BOOKS.THE first volume of the British Journal of SutrgerylO pre- sents a very handsoine.appearance owing to its amnple page, well-space.d type, and numerous illustrations.It comprises the first fouLir numbers of the periodical and contains some 750 pages.The papers7 are for the niost part of a technical sort, and will appeal mainly to operating surgeons, but each nutmber in the volume has as a frontispiece a portrait followed by a brief biography of an eminent surgeon of the past.Those in this volume are Lord Lister, John Hunter, Sir Astley Cooper, and John Abernethy.-Moreover, there are accounts of visits to certain surgical clinics at home and abroad, and some notes -anonynmous, as we observe -on " instructive
Massimo Galli
Authors: Tony Kirby
Journal: The Lancet Infectious Diseases (2020)

Massimo Galli had thought that retirement was going to arrive quietly within a couple of years. In January, 2020, Galli, who is head of the Infectious Diseases Unit at the University of Milan-affiliated Luigi Sacco Hospital in Milan, Italy, had just recovered from a pulmonary thromboembolism. But the next few months would be the most challenging of his career as the COVID-19 pandemic exploded in Italy.
The Ballistocardiogram: A Dynamic Record of the Heart Beat
Journal: JAMA (1953)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 33: Combination of Allogeneic Mesenchymal and Kidney-derived Stem Cells Promotes Kidney Repair in a Swine Model of Chronic Kidney Disease
Authors: Angela C Rieger, Bryon A Tompkins, Makoto Natsumeda, Victoria Florea, Jose Rodriguez, Marcus Rosado, Wayne Balkan, Joshua M Hare, Ivonne H Schulman
Journal: Circulation Research (2017)

Background: Chronic kidney disease (CKD) has a high prevalence (~14% of the population) and is associated with a significantly increased risk of cardiovascular disease and a 15-fold higher rate of mortality than the general population. Current therapies slow disease progression but do not repair organ damage, leading to end-stage renal disease. Stem cell therapy has the potential to promote repair via neovascularization and antifibrotic effects. We tested the renal reparative capacity of allogeneic mesenchymal stem cells (MSCs) and kidney ckit+ stem cells (c-kit) in an established swine model of CKD. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: MSC (10х10 6 ), c-kit (10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Allogeneic cell therapy was delivered via the patent renal artery of the remnant kidney. Kidney functional parameters and renal MRI were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was validated from baseline to 4 weeks by an increased creatinine: (Δ1.1 ± 0.15 mg/dl; p&lt;0.0001), BUN (Δ13.50 ± 2.99mg/dl; p=0.0003), and urine protein/creatinine ratio (Δ0.311mg/g; p=0.018), and decreased GFR (Δ49.82 ±6.41 ml/min; p=0.0002). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). BUN and creatinine levels improved in all of the groups from 4-12 weeks. GFR also improved in all the groups, but with the greatest effect in the combination group (76± 23.83ml/min; p= 0.03) from 4-12 weeks. Urine protein/creatinine ratio did not change in placebo but decreased in cell treated groups. There was no evidence of immune rejection as evaluated in a complete body necropsy. Conclusion: Allogeneic MSCs and kidney-derived stem cells are safe in a CKD swine model. The combination of stem cells was shown to be more efficacious in improving kidney function. These novel findings have important implications for the advancement of cell therapy for CKD.
Correction: Article on EphB4 Is Up-regulated in Colorectal Cancer
Journal: Cancer Research (2009)

Correction: Article on EphB4 Is Up-regulated in Colorectal CancerIn the article on how EphB4 is up-regulated in colorectal cancer in the May 1, 2009 issue of Cancer Research (1), there are errors in three of the figures.In the upper panel of Fig. 1F, the Stage 4/EphB4 bar should be black instead of blue.In Fig. 3B, all of the siRNA doses should be labeled ''nmol/L'' instead of ''mmol/L''.In the upper panel of Fig. 6D, the brown line with brown circles represents the ''Parent+ anti-TRAIL ab'' tumor, and the blue line with blue triangles represents the ''Parent'' tumor.The corrected figures appear below.