tbuckley/cabot-search huggingface dataset:
METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer
Authors: Weijun Wan, Xiang Ao, Quan Chen, Yang Yu, Luoquan Ao, Wei Xing, Wei Guo, Xiaofeng Wu, Chengxiu Pu, Xueting Hu, Zhan Li, Mengwei Yao, Donglin Luo, Xiang Xu
Journal: Molecular Cancer (2022)

Abstract Background Continual expression of PD-L1 in tumor cells is critical for tumor immune escape and host T cell exhaustion, however, knowledge on its clinical benefits through inhibition is limited in breast cancer. N 6 -methyladenosine (m 6 A) plays a crucial role in multiple biological activities. Our study aimed to investigate the regulatory role of the m 6 A modification in PD-L1 expression and immune surveillance in breast cancer. Methods MeRIP-seq and epitranscriptomic microarray identified that PD-L1 is the downstream target of METTL3. MeRIP-qPCR, absolute quantification of m 6 A modification assay, and RIP-qPCR were used to examine the molecular mechanism underlying METTL3/m 6 A/IGF2BP3 signaling axis in PD-L1 expression. B-NDG and BALB/c mice were used to construct xenograft tumor models to verify the phenotypes upon METTL3 and IGF2BP3 silencing. In addition, breast cancer tissue microarray was used to analyze the correlation between PD-L1 and METTL3 or IGF2BP3 expression. Results We identified that PD-L1 was a downstream target of METTL3-mediated m 6 A modification in breast cancer cells. METTL3 knockdown significantly abolished m 6 A modification and reduced stabilization of PD-L1 mRNA. Additionally, METTL3-mediated PD-L1 mRNA activation was m 6 A-IGF2BP3-dependent. Moreover, inhibition of METTL3 or IGF2BP3 enhanced anti-tumor immunity through PD-L1-mediated T cell activation, exhaustion, and infiltration both in vitro and in vivo. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues. Conclusion Our study suggested that METTL3 could post-transcriptionally upregulate PD-L1 expression in an m 6 A-IGF2BP3-dependent manner to further promote stabilization of PD-L1 mRNA, which may have important implications for new and efficient therapeutic strategies in the tumor immunotherapy.
Russian doctors, nurses, and paramedics demand an end to hostilities in Ukraine
Journal: BMJ (2022)

Russian doctors, nurses, and paramedics demand an end to hostilities in UkraineWe, Russian doctors, nurses, and paramedics, strongly oppose the military actions carried out by Russian armed forces on the territory of Ukraine.We are not looking for the guilty and we do not judge anyone.Our mission is to save human lives.It is difficult to imagine a profession more humane than a doctor.And now, at this difficult time for both countries, we call for an immediate cessation of hostilities and for the resolution of all political issues exclusively by peaceful means.
Human Granulocytic Ehrlichiosis—New York, 1995
Journal: JAMA (1995)

Since 1986, two human tickborne diseases caused by Ehrlichia spp. have been recognized in the United States: human monocytic ehrlichiosis (HME), caused by E. chaffeensis, and human granulocytic ehrlichiosis (HGE), caused by an agent closely related to E. equi (1,2). In June 1995, the Westchester County (New York) Department of Health (WCDOH) received reports from physicians who were treating patients for suspected HGE. In response, the WCDOH sent information to all primary-care physicians in Westchester County describing the clinical and laboratory features of ehrlichiosis (fever, myalgia, headache, leukopenia, and thrombocytopenia) and requested that they voluntarily report suspected cases of ehrlichiosis. This report summarizes an investigation by the New York State Department of Health (NYSDOH) and the WCDOH of suspected ehrlichiosis cases and the clinical characteristics of confirmed and probable cases.
Helen Salisbury: Expressing empathy
Authors: Helen Salisbury
Journal: BMJ (2022)

I spent many years as a medical teacher attempting to coach students in the art of empathy.Some needed very little prompting, instinctively knowing what to say and when to say nothing while just sitting quietly.Others were on a longer journey, needing pointers about what to actively avoid and practice in being comfortable with silence.This theory recently became reality for me from the other side of the divide.I found myself on the receiving end of a lot of sympathy and empathy and am bracing myself for more to come.As an intellectual exercise (always a useful retreat when times are hard), I have been trying to analyse what makes some expressions of empathy comforting and welcome whereas others make me inwardly cringe.Each person will have different rules, but mine go something like this:• Do not use stock phrases."I'm sorry for your loss" makes people sound as if they have escaped from an American police drama."I'm so sorry" is enough.• "I understand this is a lot for you to take in right now" suggests that someone is feeble minded as well as distressed and should be avoided at all costs.They might be too upset to remember every detail, so if they're going to need the information, write it down and give it to them to read later.• Have the confidence to be yourself; try to drop the formality and shrug off your metaphorical white coat."I am so sorry that you are having such a difficult time," is ok, but the simpler: "Sorry, this is really horrible" goes down better.• When it comes to the amount of medical detail you share, do keep checking what the patient or relative does or doesn't want to know, as people have very different needs and comfort levels.• And when you don't know what to say, that's ok.Silence is fine, as long as you don't look uncomfortable with it.If they want to talk, they will, but you don't have to encourage them to do so, or explain that there is no hurry, or tell them that you are there to listen.Don't say it, just do it.• The ritual of use of tea in the British processing of shock and grief should be respected.Preferably in proper china mugs rather than flimsy plastic cups that scald.And if this sounds too hard, don't worry.What comes through most strongly in every interaction is the underlying intent.Even if your words are clumsy and you look a bit uncomfortable, your wish to be kind will show-and in the end, that is what they will remember.
Venereal Diseases
Authors: W. A. Ketterer
Journal: JAMA (1964)

These two books by British authors provide fine treatises of current medical knowledge on venereal diseases.<i>Venereal Diseases</i>is an excellent, much needed textbook and<i>Recent Advances in Venereology</i>is a scholarly compendium of pertinent studies and literature from the postwar period through 1962. Many good photographs, including colored plates, illustrate the first text; useful references following each chapter and a few explanatory tables and graphs are included in the second. Typographical errors are extremely few. The books provide a review of the five venereal diseases and also include chapters on ophthalmia neonatorum, non-gonococcal urethritis, Reiter's disease, trichomoniasis, the treponematoses, and other genital conditions. Reiter's disease is particularly well covered in an extensive, descriptive review. The books are primarily medical in coverage with scanty material on public health aspects. Both volumes seem very conservative in many veiwpoints, both in medicine and in public health. Medically, the sections on gonorrhea therapy
Covid-19: Lagging vaccination leaves the Caribbean vulnerable, says PAHO
Authors: Luke Taylor
Journal: BMJ (2022)

The sluggish pace of covid-19 vaccination in the Caribbean is leaving the region vulnerable to current and future outbreaks of the disease, senior Pan American Health Organization (PAHO) officials have warned. 1Pan American Health Organization.The Bahamas receives covid-19 vaccines through a collaboration between PAHO/WHO, Canada, and Colombia.https://www.paho.org/en/news/28-12-2021-bahamas-receives-covid-19vaccines-through-collaboration-between-pahowho-canada-and 4
From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults
Journal: JAMA (1993)

The Centers for Disease Control and Prevention (CDC) has revised the classification system for HIV infection to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions. This classification system replaces the system published by CDC in 1986 and is primarily intended for use in public health practice. Consistent with the 1993 revised classification system, CDC has also expanded the AIDS surveillance case definition to include all HIV-infected persons who have less than 200 CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte percentage of total lymphocytes of less than 14. This expansion includes the addition of three clinical conditions--pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer--and retains the 23 clinical conditions in the AIDS surveillance case definition published in 1987; it is to be used by all states for AIDS case reporting effective immediately.
Yellow Fever.
Journal: JAMA (1883)

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
Correction to: Whole genome sequencing-based classifcation of human-related Haemophilus species and detection of antimicrobial resistance genes
Authors: Margo Diricks, Thomas A. Kohl, Nadja Käding, Vladislav Leshchinskiy, Susanne Hauswaldt, Omar Jiménez Vázquez, Christian Utpatel, Stefan Niemann, Jan Rupp, Matthias Merker
Journal: Genome Medicine (2022)
NECROLOGY.
Journal: JAMA (1897)

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
Enhancing demethylation-induced differentiation in IDH-mutant glioma
Authors: Julie J Miller, Daniel P Cahill, Isabel Arrillaga-Romany
Journal: Neuro-Oncology (2022)

Elevated levels of D-2-hydroxyglutarate (2HG) produced by mutant IDH1 or IDH2 enzymes have been shown to have a role in establishing the glioma CpG island methylator phenotype (G-CIMP), characterized by pathogenic global hypermethylation.1–3 As an oncometabolite, 2HG inhibits a wide array of α-ketoglutarate-dependent dioxygenases, a subset of which normally function as DNA and histone demethylases. A 2HG-induced change in the epigenetic landscape contributes to gliomagenesis, with the disruption of typical modes of gene regulation causing an impairment to differentiation and aberrant maintenance of a glioma stem-cell program. Despite these substantial advances in understanding of IDH-mutant glioma development, the progress in developing effective, IDH-mutant-specific therapies remains limited, with the current standard of care continuing to be comprised of radiation therapy and chemotherapeutics. The demethylating agents 5-azacytidine (5-aza) and decitabine (DAC) are DNA methyltransferase 1 (DNMT1) inhibitors that are under investigation for the treatment of IDH-mutant glioma. Both agents have demonstrated efficacy in slowing tumor growth and prolonging survival in IDH-mutant glioma xenograft models.4–6 In this issue of Neuro-Oncology, da Costa Rosa et al now show enhanced effectiveness of this approach with the addition of pro-differentiation agent all-trans retinoic acid (atRA), an agent that is used clinically to promote terminal differentiation in the treatment of acute promyelocytic leukemia (APL).7
NEW ZEALAND RHEUMATISM ASSOCIATION: Annual Conference, Wellington, October 12-14, 1967
Journal: Annals of the Rheumatic Diseases (1968)

The presidential address was given by Dr. I. C. Isdale (Rotorua), who took as his subject "Aetiolo- gical Classifications of Osteoarthritis of the Hip": The clinical and radiological diagnosis of the disease was described and the causes of its various features, such as bone cysts and femoral head deformity, discussed.Possible initiating conditions were proposed, including ischaemia, minor degrees of slipped femoral epiphysis, and acetabular dysplasia.The following papers were presented:Diagnostic Problem presenting as Shoulder-Hand Syndrome.D. A. BALLANTYNE (Hastings): A 60-yearold man, with a 20-year history of epilepsy treated with phenobarbitone, phenytoin, and primidone, had a 14- month history of shoulder pain progressing to bilateral shoulder-hand syndromes.There was co-existent thyrotoxicosis.The erythrocyte sedimentation rate was normal rheumatoid factor negative, and radiography revealed only mild cervical degenerative changes.Skin biopsy for scleroderma and barium swallow were noncontributory.Crystal Synovitis and Periarticular Calcification.D. E. CAUGHEY (Auckland): The clinical syndromes asso- ciated with the deposition of calcium pyrophosphate dihydrate and hydroxy apatite around joints were illustrated by two cases.A third case with calcifying periarthritis had multiple peripheral and central joints involved.Tendons, ligaments, and cartilages were calcified.This patient did not seem to fit into the groups previously reported.The calcium deposits were not examined by x-ray diffraction.Crico-arytenoid Arthritis.D. E. CAUGHEY (Auckland): Eight cases of longstanding arthritis presented with suggestive symptoms.One, with morning stiffness involving crico-arytenoid joints, was found to have a fixed vocal cord on one side and impeded movement of the other cord.Another patient with intermittent pains in the throat and huskiness over 3 years had a nodule in the region of the crico-arytenoid joint present for 2 months.Of the remaining four patients who had laryngoscopy performed, one showed evidence of redness and swelling around the crico-arytenoid joints but the other three were normal on examination.The loss of range in the singing voice was often an early symptom indicating that these joints were affected by rheumatoid disease.
Leprosy Prophylaxis
Authors: Paul Fasal
Journal: JAMA (1967)

Leprosy is not a major public health problem in J the continental United States. However, approximately 2,000 cases of leprosy are known to exist in persons living here. The time lag between the appearance of symptoms of leprosy and the establishment of the correct diagnosis and institution of treatment in this country is frequently prolonged because the index of suspicion is low.<sup>1,2</sup>Consequently, at the time of diagnosis, family members of the persons found to be suffering from leprosy may have been exposed to the disease for prolonged periods of time. At the Leprosy Clinic of the US Public Health Service Hospital in San Francisco, 166 cases of leprosy were seen during the past seven years. Of 198 family contacts of patients with lepromatous disease examined at the clinic, 16 developed leprosy. This represents an attack rate of 80.8 per 1,000 contacts examined. Until recently, the policy at the
Risk factors for HCC in contemporary cohorts of patients with cirrhosis
Authors: Fasiha Kanwal, Saira Khaderi, Amit G. Singal, Jorge A. Marrero, Nicole Loo, Sumeet K. Asrani, Christopher I. Amos, Aaron P. Thrift, Xiangjun Gu, Michelle Luster, Abeer Al‐Sarraj, Jing Ning, Hashem B. El‐Serag
Journal: Hepatology (2022)

Background and Aims: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk. Approach and Results: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% had cured HCV, 16.1% had alcoholic liver disease, and 30.1% had NAFLD. During 7406 person‐years of follow‐up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% CI, 1.51–2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2‐fold higher in patients with cured HCV (HR, 2.04; 95% CI, 1.24–3.35). Current smoking (HR, 1.63; 95% CI, 1.01–2.63) and overweight/obesity (HR, 1.79; 95% CI, 1.08–2.95) were also associated with HCC risk. Conclusions: HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower risk in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.
Checkpoint Inhibitors Spur Changes in Trial Design
Journal: Cancer Discovery (2017)

Given the success of checkpoint inhibitors and the desire to test them in combination with other immunotherapies and targeted therapies, hundreds of clinical trials have been launched. To most efficiently study these agents, researchers and the FDA are exploring the use of novel endpoints, the use of new preclinical models, and adaptive trial designs. However, the cost and demands associated with the conduct of increasingly sophisticated early-phase clinical trials are putting smaller companies and some academic medical centers at a disadvantage.
Nonocclusive Mesenteric Ischemia
Authors: L. Brandt
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
SELECTIONS.
Journal: JAMA (1895)

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
Mondor's disease and string phlebitis
Authors: D. J. Abramson
Journal: JAMA (1966)

MONDOR'S DISEASE, or string phlebitis of the chest wall, is relatively unknown, often unrecognized, and infrequently reported. The development of a fibrous cord in the region of the breast is of great concern to the patient. Therefore, it is important that this lesion be recognized as benign and selflimited and not as an indication of malignancy. The following cases draw attention to this entity and its clinical features. Methods of treatment, including the forcible snapping of the band, will be described. (Priority for this technique is given to Frederick Y. Donn, MD, Washington, DC, who initially used this procedure [F. Y. Donn, personal communication]. ) <h3>Report of Cases</h3><h3>Case 1.—</h3> A 32-year-old Negro woman complained of soreness and a band in the right outer chest wall, that had been present for two weeks. She was eight weeks post partum. A fibrous cord was found in the outer quadrant of the breast,
Oncology Drug Shortages Persist
Journal: Cancer Discovery (2019)

Abstract Drug shortages in oncology have been an ongoing issue in the United States, leaving clinicians scrambling to ensure that patients have access to therapies. Depleted drug supplies have been particularly acute in pediatric oncology, and a recent shortage of vincristine demonstrates how shortages occur and how treatment centers respond—and highlights the need for better strategies to avoid or mitigate such situations.
Physicians' Reaction to Chernobyl Explosion: Lessons in Radiation—and Cooperation
Journal: JAMA (1986)

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