tbuckley/cabot-search huggingface dataset:
Efficacy, safety, and biomarker analysis of neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx).
Authors: Axel Bex, Yasmin Abu-Ghanem, Johannes V. Van Thienen, Niels Graafland, Brunolf Lagerveld, Patricia Zondervan, Harrie Beerlage, Jeroen van Moorselaar, Mark Kockx, Pieter-Jan Van Dam, Bernadett Szabados, Christian U. Blank, Thomas Powles, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2022)

289 Background: Antibodies targeting PD-1/PD-L1 combined with vascular endothelial growth factor (VEGF) inhibitors are a first-line standard of care for metastatic RCC. Neoadjuvant use of these combinations may lead to downstaging and reduce the risk of recurrence. In addition, sequential tissue may allow identification of key immune biomarkers associated with outcome. Methods: Neoavax is a single arm phase II trial of 12 weeks neoadjuvant avelumab/axitinib prior to nephrectomy in 40 pts with high-risk non-metastatic clear-cell (cc) RCC (cT1b-4cN0-1M0, Grades 3-4). Primary endpoint is RECIST 1.1 partial response (PR) in the primary tumour (PT) in ≥25%. Secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. Biomarker analysis on sequential tissue is an exploratory endpoint. Expression of PD-L1 (SP263), CD8+, CD8-granzyme-B (CD8/GZMB)+, Foxp3+ cells, CD8/CD39+ and MHC-I were compared on pre-treatment biopsy and nephrectomy samples from 34 pts (NCT03341845). Results: Pts/tumour characteristics are shown in table. Twelve pts (30%) had a PR of the PT from a baseline mean diameter of 10.3 (range 5.6-16.4) cm. Median PT downsizing was 20 (0-43.5) % and median post-treatment vital tumour presence was 50 (1-100) %. At a median follow-up of 23.5 months, recurrence occurred in 13 (32%) pts at a median of 8 (2-23) months and 3 died of disease. Of the 12 pts with PT PR, 11 (92%) are disease-free. Median DFS and OS are not reached. Postoperative adverse events occurred in 8 pts (2 Clavien Dindo grade 3a). There were no treatment-related surgery delays and no PT progression. Post-treatment samples showed upregulation of PD-L1 expression (p &lt;0.0001) and total CD8+ densities (p &lt; 0.01) when compared to pre-treatment biopsies. Comparing samples of pts with PR vs no PR in the PT, no clear immune marker differences were observed. Post-treatment samples from pts that recurred were characterized by lower densities of total, intra-epithelial and stromal CD8+, intra-epithelial CD8+CD39+ (p&lt;0.05) and total CD8+GZMB+ (p=0.1). Pre-treatment biopsies showed no clear differences. Conclusions: Neoadjuvant avelumab/axitinib for non-metastatic high-risk RCC leads to PR of the PT in 30% which is associated with DFS. Pts without recurrence had a significant increase in CD8+ densities compared to pts with recurrence suggesting expansion of a pre-existing immune response. Clinical trial information: NCT03341845. [Table: see text]
Tubercle Bacillus.
Authors: M. V. Ball
Journal: JAMA (1898)

Warren, Pa., Feb. 12, 1898. <h3>To the Profession:</h3> —Any physician knowing of cases in which tubercle bacilli were found in the sputum, without any other physical evidence of disease in the lungs, and having seen such cases for a period of several years, noticed no further progress of the disease, will confer a great favor on the undersigned by reporting the same to him. I desire to obtain evidence on the import of bacillus tuberculosus in the sputum.
Cutaneous sarcoidosis in venepuncture sites.
Authors: Lino Rossi, G Gresham
Journal: BMJ (1973)

the system in the ventricular septum were also severely affected, further establishing the aetiology of the heart block.These findings are characteristic of the lesions and the functional impairment that I ~~~~M-'~1 ~~~~F ig 2-The node of Tawara, recognizable above the dark-stained central fibrous body, almost completely replaced by sarcoid granulomatous tissue.(Azanx18.)seems to be peculiar to sarcoid heart disease, as stated in your leading article.-Iam, etc.,
Cutaneous polyarteritis.
Authors: T Dyk
Journal: BMJ (1973)

glycaemia.1This insulin-induced hypogly- caemia activates the corticotrophin releasing factor-corticotrophin-glucocorticoid axis.This permanent stimulation is afterwards responsible for the steady hypercorticism in obesity.Glucocorticoids as well as other anti- insulin factors, involve tissue insulin resistance and hyperglycaeniia which, by stimulating the /-cells result in their hyperplasia.Thus the chain of pathogenesis of obesity may be shown as follows: :-cells hyper- sensitivity to carbohydrates-postprandial hyperinsulinism-postprandial hypoglycaem- ia-hypercorticism-tissue resistance to insulin and hyperglycaemia-A-cell hyperplasia.The energy imbalance with predom- inant intake is a result of intensive lipogenesis resulting from hyperinsulinism.Excessive insulin response to glucose load in obese subjects is well known.But for the successful prevention of obesity it is neces- sary to separate the "pre-obese" subjects.This group consists of the patients with normal weight and excessive insulin response to glucose load.-Weare, etc.,
Deep learning in image-based breast and cervical cancer detection: a systematic review and meta-analysis
Authors: Peng Xue, Jiaxu Wang, Dongxu Qin, Huijiao Yan, Yimin Qu, Samuel Seery, Yu Jiang, Youlin Qiao
Journal: npj Digital Medicine (2022)

Accurate early detection of breast and cervical cancer is vital for treatment success. Here, we conduct a meta-analysis to assess the diagnostic performance of deep learning (DL) algorithms for early breast and cervical cancer identification. Four subgroups are also investigated: cancer type (breast or cervical), validation type (internal or external), imaging modalities (mammography, ultrasound, cytology, or colposcopy), and DL algorithms versus clinicians. Thirty-five studies are deemed eligible for systematic review, 20 of which are meta-analyzed, with a pooled sensitivity of 88% (95% CI 85-90%), specificity of 84% (79-87%), and AUC of 0.92 (0.90-0.94). Acceptable diagnostic performance with analogous DL algorithms was highlighted across all subgroups. Therefore, DL algorithms could be useful for detecting breast and cervical cancer using medical imaging, having equivalent performance to human clinicians. However, this tentative assertion is based on studies with relatively poor designs and reporting, which likely caused bias and overestimated algorithm performance. Evidence-based, standardized guidelines around study methods and reporting are required to improve the quality of DL research.
Rubella vaccination.
Authors: S Rowlands
Journal: BMJ (1979)

technique; and modem techniques using the gamma-camera, 99mTc-MAA, and oblique views3 would be expected to give greater reproducibility.Surely, given these data, the statement that the lung scans "correlated poorly with the results of pulmonary angiography" should be reversed to say that the interpretation of pulmonary angiograms even by experts was, to say the least, difficult and correlated poorly with the findings of perfusion lung scanning.
For and Against Routine Removal of Peripheral Intravenous Catheters
Authors: Claire M. Rickard, David L. Paterson, Vineet Chopra
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Internal Medicine journal
Lactobacillus reuteri—an old acquaintance takes on a new task in colorectal tumor surveillance
Authors: Christina Watschinger, Alexander R Moschen
Journal: Cancer Cell (2022)

In this issue of Cancer Cell, Bell et al. identify the commensal bacterium Lactobacillus reuteri and its major metabolite reuterin as an important gatekeeper and promising target in colorectal cancerogenesis. They decipher a metabolic interplay in which L. reuteri is suppressed by metabolites from dysplastic intestinal epithelial cells which in turn are highly sensitive to the oxidative effects of the electrophile reuterin.
Turing milk into pro-apoptotic oral nanotherapeutic: <i>De novo</i> bionic chiral-peptide supramolecule for cancer targeted and immunological therapy
Authors: Wangxiao He, Zhang Zhang, Wenguang Yang, Xiaoqiang Zheng, Weiming You, Yu Yao, Jin Yan, Wenjia Liu
Journal: Theranostics (2022)

Chirality in biomolecules is ubiquitous in our world, but oral nanomedicines constructed from chiral peptides are extremely rare, principally because of the immature nanofabrication and inadequate bioavailability of chiral nanostructures.Methods: To realize the oral administration of chiral peptides and break through their forbidden zone in intracellular space, a chiral-peptide supramolecular (DPAICP) camouflaging with the membrane from milk-derived extracellular vesicles (ME) was developed herein through an aqueous-based growth method of chiral peptide Au(I) infinite covalent polymer (DPAICP) involving in organothiol D-peptides and Au 3+ , and a feasible camouflage technology using ME.Results: DPAICP@ME possessed favorable pharmaceutical properties to remain stable during the gastrointestinal absorption and blood circulation, and showed the satisfactory tumor accumulation through oral medication.Expectedly, oral DPAICP@ME played its predetermined role in vivo to restore p53 signaling pathway for cancer therapy in B16F10 homograft malignant melanoma model, LLC Lewis orthotopic transplantation model of lung cancer and patient-derived orthotopic xenograft (PDOX) mice model of colon cancer.Moreover, oral DPAICP@ME augmented the action of immunotherapy by Anti-PD1 through the further T-cell activation. Conclusion:The de novo design of the bionic chiral-peptide supramolecule provides a practicable strategy for the construction of biomimetic chiral peptide-derived nanostructures that can be taken orally, and likely boosts chiral nanomedicine discovery efforts for a wider range of diseases including cancer.
MOTOR NOTES FOR MEDICAL MEN
Authors: H. M. Buist
Journal: BMJ (1920)

THERE is sucll an unprecedented variety of mnotor carriages at the M1Iotor Show organized at Olymipia and tIme White City by the Society of Mot6r MIanufacturers and Traders, under thle patronage of the King, tllat the mnedical man is in sore need of some guide to those features likely to appeal to hiim.Tlho display is, internationially, tlhe most representative organized in any part of the world.It replaces the yearly slhow in Paris, wljicll was not lheld last montl.It precedes the great American slhows.Tlherefore, for tlle time being, London is the miotor mnart of the world.Late enemy countries excepted, the industry of every country taking a part of any imnportance in motor building is adequately represented, the nuinber of American makes on the market being particularly noteworthy.Time exlhibition is marked by tlle introduction of a large nunmber of entirely new makes of cars, but a goodly proportion of tllem have not adequate m-anufacturing facilities belind them to justify tlleir receiving tIme patronage of the medical profession, whose prime need is a tested design offered by financially well-establislhed firms; reliability and economy of cost, together witlh absence of the speculative elemnelnt, are essential to doctoms' service.Last year 271 makes of cars were on the Britislh marliet.According to the Autocar, that nLiruber of builders and assenmblers has now risen to 302, of wlhiclh 149, or less than half, are Britislh.Tlle varieties of types at tlle current exhibition nunuber 459, because many of thle makers mal-ket more than one model.
Prevention and Treatment of Lyme Disease
Authors: Cynthia T. Nguyen, Adam S. Cifu, David Pitrak
Journal: JAMA (2022)

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
The Doctor and Citizenship
Journal: JAMA (1934)

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
AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper
Authors: Christoph Bergmann, Aurélie Poli, Ioana Agache, Rodolfo Bianchini, Heather J. Bax, Mariana Castells, Silvia Crescioli, David Dombrowicz, Denisa Ferastraoaru, Edda Fiebiger, Hannah J. Gould, Karin Hartmann, Elena Izquierdo, Galateja Jordakieva, Debra H. Josephs, Marek Jutel, Francesca Levi‐Schaffer, Leticia de las Vecillas, Michael T. Lotze, Gabriel Osborn, Mariona Pascal, Frank Redegeld, David Rosenstreich, Franziska Roth‐Walter, Carsten Schmidt‐Weber, Mohamed Shamji, Esther H. Steveling, Michelle C. Turner, Eva Untersmayr, Erika Jensen‐Jarolim, Sophia N. Karagiannis
Journal: Allergy (2022)

The immune system interacts with many nominal 'danger' signals, endogenous danger-associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)-associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti-cancer immune and targeted therapies. Cross-disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes.
PPARγ deacetylation dissociates thiazolidinedione’s metabolic benefits from its adverse effects
Authors: Michael J. Kraakman, Qiongming Liu, Jorge Postigo-Fernandez, Ruiping Ji, Ning Kon, Delfina Larrea, Maria Namwanje, Lihong Fan, Michelle Chan, Estela Area-Gomez, Wenxian Fu, Remi J. Creusot, Li Qiang
Journal: Journal of Clinical Investigation (2018)

Thiazolidinediones (TZDs) are PPARγ agonists with potent insulin-sensitizing effects. However, their use has been curtailed by substantial adverse effects on weight, bone, heart, and hemodynamic balance. TZDs induce the deacetylation of PPARγ on K268 and K293 to cause the browning of white adipocytes. Here, we show that targeted PPARγ mutations resulting in constitutive deacetylation (K268R/K293R, 2KR) increased energy expenditure and protected from visceral adiposity and diet-induced obesity by augmenting brown remodeling of white adipose tissues. Strikingly, when 2KR mice were treated with rosiglitazone, they maintained the insulin-sensitizing, glucose-lowering response to TZDs, while displaying little, if any, adverse effects on fat deposition, bone density, fluid retention, and cardiac hypertrophy. Thus, deacetylation appears to fulfill the goal of dissociating the metabolic benefits of PPARγ activation from its adverse effects. Strategies to leverage PPARγ deacetylation may lead to the design of safer, more effective agonists of this nuclear receptor in the treatment of metabolic diseases.
Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in Japan
Authors: Hironari Shiwaku, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Junya Shiota, Chiaki Sato, Masaki Ominami, Hiroyuki Sakae, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Hiroshi Yokomichi, Suguru Hasegawa, Haruhiro Inoue
Journal: Endoscopy (2022)

Abstract Background Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM. Methods This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD. Results Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy &gt; 10 cm (RR 1.12), and gastric myotomy &gt; 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy &gt; 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (P = 0.04), particularly in PPI users (P &lt; 0.001). Conclusions The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.
Abstract 17284: Clinical Characteristics and Management of Patients With Heart Failure With Mid-Range Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Carlos A Godoy Rivas, Samuel Urrutia, Eleazar Montalvan, Mario Rodriguez, Eduardo Venegas, Marian Simonson, Eiran Gorodeski, Chadi G Ayoub, Haitham G Ahmed
Journal: Circulation (2018)

Introduction: Heart Failure (HF) is categorized according to the AHA/ACC 2013 HF Guidelines based on Left Ventricular Ejection Fraction (LVEF); HF with Reduced Ejection Fraction (HFrEF, EF≤40%), and HF with preserved EF (HFpEF, EF ≥ 50%). There is a group of “borderline” patients with EF 41%-49%, termed Heart Failure with Mid-Range Ejection Fraction (HFmrEF). Given this category is not well understood, we sought to evaluate clinical characteristics and management patterns for patients with HFmrEF. Methods: A systematic review was performed using Ovid MEDLINE, EMBASE, Cochrane CENTRAL and LILACS (1946 – 03/2018). Search terms included HF, mid-range, borderline LVEF with several ranges (40-50 or 40-45 or 45-50). Variables characterizing clinical features and medications were extracted for each HF group and adjusted odds ratios (ORs) were pooled. Results: Of 1,131 abstracts identified, 24 met inclusion criteria (total patients 480,188). Patients with HFmrEF compared to those with HFrEF were more likely to be female (OR 1.42), have hypertension [HTN] (OR 1.34) and diabetes (OR 1.11), higher SBP (OR 1.17), better NYHA-FC (FC I OR 1.73, FC II 1.33), less likely to have coronary artery disease [CAD] (OR 0.74) and more likely to be treated with ACEI, ARB, BB, Digoxin, MRA and statins (Figure 1-2). HFmrEF patients when compared to those with HFpEF were less likely to be female (OR 0.54) or have HTN (OR 0.68), and more likely to have CAD (OR 1.25), and to be treated with HF medications and statins. Conclusions: Patients with HFmrEF have higher SBP and better NYHA-FC (I and II) compared to HFrEF patients and are less likely to be female and more likely to have CAD compared to HFpEF patients. Further research is needed to help guide management in this unique but clinically important population. Figure 1A. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFrEF vs HFmrEF patients Figure 1B. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFmrEF vs HFpEF patients Figure 2A. Forest plot of adjusted ORs comparing medications used in HFrEF vs HFmrEF patients Figure 2B. Forest plot of adjusted ORs comparing medications used in HFmrEF vs HFpEF patients