tbuckley/cabot-search huggingface dataset:
Evaluation of tumor genomic variants in Japanese patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide: Protocol of a phase 4 study (CUARTET).
Authors: Hirotsugu Uemura, Toshiyuki Kamoto, Hiroji Uemura, Naoya Masumori, Naoki Terada, Shusuke Akamatsu, Yosuke Koroki, Shintaro Ono, Miku Ito, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2022)

TPS196 Background: Apalutamide is an oral non-steroidal, potent, and highly selective androgen receptor antagonist. Alterations in androgen signaling, DNA repair, and other pathways impact on castration sensitivity and outcomes of androgen antagonists. Currently, there is limited data on the types or effects of variants in prostate cancer (PC)-related genes among Japanese mCSPC (castration-naïve or castration-sensitive) patients treated with apalutamide. Methods: CUARTET is a collaborative phase 4 study with a primary objective of evaluating genomic variants in 73 PC driver genes during apalutamide treatment and hence identify potential biomarkers. Men aged ≥20 years with mCSPC scheduled to start apalutamide at 20 participating institutions will be eligible. Patients previously treated with abiraterone, docetaxel, enzalutamide, apalutamide or darolutamide, are ineligible, as are those who received androgen-deprivation therapy or combined androgen blockade for &gt;6 months before registration or neoadjuvant/adjuvant hormonal therapy for &gt;36 months. The primary endpoint is the changes in genomic variants of 73 PC driver genes between pre- and post-treatment of apalutamide. Secondary endpoints, stratified by baseline genomic variants, include the proportion of patients with nadir prostate–specific antigen (PSA) ≤0.2 ng/mL, PSA–progression-free survival (PFS), PFS, overall survival, time to castration resistance, and PFS2. Other planned outcomes include safety, incidence/severity of apalutamide-related skin rash stratified by single nucleotide polymorphisms or human leukocyte antigen typing, and clinical outcomes in patients with only distant lymph node metastases. The first patient was enrolled in December 2020, and it is expected to enroll 100 patients during the 1.5-year registration period. Eighty-one patients have been enrolled in this study by July 2021. The patients will be followed up for a maximum of 4.5 years. Interim analyses are planned after the last patient has been registered. Results of CUARTET are expected to reveal the genomic variants, including those in androgen signaling-related genes, that are potentially involved in acquired resistance to apalutamide. The results will reveal biomarkers to aid treatment decision making for mCSPC patients, including the treatment options following apalutamide. Clinical trial information: NCT04601441.
Real-world evidence from a single U.K. cancer center for atezolizumab in second-line setting in advanced urothelial cancer: Moving beyond clinical trials.
Authors: Syed A. Hussain, Muneeb Qureshi, Bilal Tahir, Ahmed Rehan, James W.F. Catto
Journal: Journal of Clinical Oncology (2022)

461 Background: Atezolizumab is approved for use in advanced urothelial cancer in second line setting after platinum based chemotherapy. We conducted a retrospective study to evaluate clinical outcomes in patients treated in a single UK cancer centre with Atezolizumab for advanced urothelial cancer. Methods: Data was collected from electronic records for patients treated with Atezolizumab for advanced urothelial cancer patients between January 2019 to June 2021. Patients with histologically proven advanced urothelial cancer, PS 0-1, GFR &gt; 30 ml/min by Cockcroft-Gault formula, who had progressed after platinum based chemotherapy were eligible. Maximum duration of treatment allowed was 24 months as per National Cancer Drugs Fund criteria. Initially 3 weekly cycles using Atezolizumab at a dose of 1200 mg was used, patients received 4 weekly dose once 1680 mg dose was available. Kaplan Meier survival estimates were used to calculate progression free survival and overall survival. Results: 32 patients received Atezolizumab between Jan 2019 to June 2021. The mean age was 70.6 years (range 44-88). 10 patients had ECOG PS 0, 22 patients had PS 1. Male 19, Female 13. At the time of analysis, 9 out of 32 patients were alive, 2 patients had completed 24 months of treatment and had no evidence of disease progression. Total 297 cycles of Atezolizumab were delivered (190 cycles were delivered at 3 weekly intervals, while 107 were delivered 4 weekly). The median progression free survival was 24.290 weeks (95% CI: 23.202-25.378), and the median overall survival was 40.860 weeks (95% CI: 19.788-61.932). 10 patients (31.2%) were alive at 12 months, 8 patients (25%) were alive at 18 months. The number of patients with toxicity of grade ≥3 were 4.There were no treatment related deaths. Conclusions: Atezolizumab is effective and well tolerated in patients with advanced urothelial cancer in second line setting. Durable responses were noted with 25% of patients alive at 18 months.
Style.
Authors: S K Pandya
Journal: BMJ (1987)

of a book or in a table of contents?What, on the other hand, makes us groan, shift weight from one ischial tuberosity to the other with increasing frequency, and, against ingrained politeness, walk out while a lecturer is still on his feet flashing slides of varied hue on the screen?Why does the same subject taught by one evoke applause and by another, boos and cat calls?Style, the pedant tells us, is what makes the difference.He goes on to say that style comprises the collective characteristics of the writing, diction, or presentation (ofdata, concept, or opinion) of an individual.The cultivation of style, then, has as its goals sparkling speech and captivating prose.To reach these goals we must learn to dress our thoughts simply and effectively and in doing so may have to change the habits ofour minds.
Comment: radiosensitization and the selective effect
Authors: P. Rubin
Journal: JAMA (1971)

The ideal in the treatment of malignant disease is achieved when the cancer is completely eradicated and the surrounding normal tissue shows no evidence of structural or functional injury. In clinical practice, this ideal selective effect is seldom achieved; a certain degree of residual damage must be accepted as a sequel to the destruction of a lethal tumor. The extent of alterations of normal tissues that is acceptable varies in different anatomic settings, but the integrity of the vital structures must be maintained. This ideal has been described as the "selective effect" when it is applied to radiation therapy. One of the major frontiers of radiation biologic research is to make irradiation more selective. The term, "radiosensitization" has been used to describe the modification of the radiation response by agents; it broadly includes mechanisms of enhancement, such as additivity, synergism, or time dose modification. No specific radiation effect that is
PUBLIC HEALTH.
Journal: JAMA (1896)

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
Neutralization and durability of 2 or 3 doses of the BNT162b2 vaccine against Omicron SARS-CoV-2
Authors: Hongjie Xia, Jing Zou, Chaitanya Kurhade, Hui Cai, Qi Yang, Mark Cutler, David Cooper, Alexander Muik, Kathrin U. Jansen, Xuping Xie, Kena A. Swanson, Pei-Yong Shi
Journal: Cell Host & Microbe (2022)
Paradoxical Embolism
Authors: C. A. Birch
Journal: BMJ (1945)

Patients tage of Acute Rate Total Retention Perurethral prostatectomy 621 70 97% 228 (35-11%) 3-7% (23) Suprapubic prostatectomy 131 14-97% 67 (51-15%) 2-29%/ (3) Modified Freyer's (2-stage) 49 27 -Harris's (a) I-stage 21 5 -(b) 2-stage 61 35 3 Permanent suprapubic cystostomy .9410-74% 68 (72-34%) 11-7%/ (11) No operation .. 29 3 32%.Transferred to a chronic ward Mortality from all causes following prostatectomy is 3 4%/ in a consecutive series of 752 cases.Mortality of the last 439 perurethral prostatectomies in this series = 2 51%.Of all prostatectomies 82 6% were performed perurethrally, 17-4% by various suprapubic methods.The oldest patient subjected to peruretlhral operation was aged 90.TABLE II Reasons for LeavingTPermanent No. of Reasons for Not Operating No. of Suprapubic Cystostomies Cases at All Cases*
Dysmenorrhoea.
Authors: G W Theobald
Journal: BMJ (1967)

types suggests that these facts are causally related.Coughing, a regular accompaniment of smoking in many people, may be a con- tributory factor in the detachment of ciliated epithelium.These may be some of the " other possible factors " postulated by Dr. Glass to which smokers are more liable than non-smokers.-Iam, etc., Glasgow W.2.
On Locomotor Ataxy
Authors: J. L. Clarke
Journal: BMJ (1869)

I HAVE a few remarks to make on the pat/ological physiologi' of loco- motor ataxy-that is, on those al wormal actions of the spinal cord and voluntary muscles that are productive of incoordinate movements.These incoordinate movements have been, by different writers, attributed chiefly to cutaneous and muscular amtesthesia, as well as to loss of the so-calledmuscular sense; and differeint authors havegiven different degrees of prominence and importalnce to one or other of these morbid condlitions.But the lesions of the spinal cord peculiar to locomotor ataxy induce, in some of the voluntary miiscles, a certain abnormal condition which seems to have been entirely overlooked, but which appears to be really one of the chief causes of muscular iincoordination.It is the opinion of some physiologists, that the loss of muscular coordination depends on the loss of reflex action in the spinial cord; and, since the posterior columns of the spinal cor-d are more or less damaged in locomotor ataxy, it has been inferred that spinal reflex action is dependent on the proper fibres of the posterior columns.B3ut reflex action really depends oin excitation of the grey substance by the posterior roots of the nerves, and the reflexion of the nerv e-force so generated on to some of the miotor-nerves.Now, before I began my researches on the structure of the spinal cord, it was universally taught, both in England and abroad, that the posterior roots of the sl)inal nerves are attached exciii- sively to the lateral columns of the cord; wlhereas I showed-what is now universaily admitted-that they are attached immediately to the p5osterior columns, and no(i (it all to the lateral.The importance of this fact, in both a physiological ai( a pathological point of viewv, and especially in its relation to locomotor ataxy, will be presently made evident.In Fig. 2, whiclh represenits a transverse section of the left
Integrated Genomic Analysis Identifies <i>UBTF</i> Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia
Authors: Masayuki Umeda, Jing Ma, Benjamin J. Huang, Kohei Hagiwara, Tamara Westover, Sherif Abdelhamed, Juan M. Barajas, Melvin E. Thomas, Michael P. Walsh, Guangchun Song, Liqing Tian, Yanling Liu, Xiaolong Chen, Pandurang Kolekar, Quang Tran, Scott G. Foy, Jamie L. Maciaszek, Andrew B. Kleist, Amanda R. Leonti, Bengsheng Ju, John Easton, Huiyun Wu, Virginia Valentine, Marcus B. Valentine, Yen-Chun Liu, Rhonda E. Ries, Jenny L. Smith, Evan Parganas, Ilaria Iacobucci, Ryan Hiltenbrand, Jonathan Miller, Jason R. Myers, Evadnie Rampersaud, Delaram Rahbarinia, Michael Rusch, Gang Wu, Hiroto Inaba, Yi-Cheng Wang, Todd A. Alonzo, James R. Downing, Charles G. Mullighan, Stanley Pounds, M. Madan Babu, Jinghui Zhang, Jeffrey E. Rubnitz, Soheil Meshinchi, Xiaotu Ma, Jeffery M. Klco
Journal: Blood Cancer Discovery (2022)

Abstract The genetics of relapsed pediatric acute myeloid leukemia (AML) has yet to be comprehensively defined. Here, we present the spectrum of genomic alterations in 136 relapsed pediatric AMLs. We identified recurrent exon 13 tandem duplications (TD) in upstream binding transcription factor (UBTF) in 9% of relapsed AML cases. UBTF-TD AMLs commonly have normal karyotype or trisomy 8 with cooccurring WT1 mutations or FLT3-ITD but not other known oncogenic fusions. These UBTF-TD events are stable during disease progression and are present in the founding clone. In addition, we observed that UBTF-TD AMLs account for approximately 4% of all de novo pediatric AMLs, are less common in adults, and are associated with poor outcomes and MRD positivity. Expression of UBTF-TD in primary hematopoietic cells is sufficient to enhance serial clonogenic activity and to drive a similar transcriptional program to UBTF-TD AMLs. Collectively, these clinical, genomic, and functional data establish UBTF-TD as a new recurrent mutation in AML. Significance: We defined the spectrum of mutations in relapsed pediatric AML and identified UBTF-TDs as a new recurrent genetic alteration. These duplications are more common in children and define a group of AMLs with intermediate-risk cytogenetic abnormalities, FLT3-ITD and WT1 alterations, and are associated with poor outcomes. See related commentary by Hasserjian and Nardi, p. 173. This article is highlighted in the In This Issue feature, p. 171.
Prolonged Survival of Rat Islet Cells in Diabetic Mice Offers Hope
Journal: JAMA (1980)

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
Decitabine and vorinostat with <scp>FLAG</scp> chemotherapy in pediatric relapsed/refractory <scp>AML</scp>: Report from the therapeutic advances in childhood leukemia and lymphoma (<scp>TACL</scp>) consortium
Authors: Lauren Pommert, Eric S. Schafer, Jemily Malvar, Nathan Gossai, Ellynore Florendo, Kirthi Pulakanti, Katelyn Heimbruch, Cary Stelloh, Yueh‐Yun Chi, Richard Sposto, Sridhar Rao, Van Thu Huynh, Patrick Brown, Bill H. Chang, Susan I. Colace, Michelle L. Hermiston, Kenneth Heym, Raymond J. Hutchinson, Joel A. Kaplan, Rajen Mody, Tracey A. O'Brien, Andrew E. Place, Peter H. Shaw, David S. Ziegler, Alan Wayne, Deepa Bhojwani, Michael J. Burke
Journal: American Journal of Hematology (2022)

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (<0.1%) by centralized flow cytometry and 84% (n = 16) successfully proceeded to hematopoietic stem cell transplant. Two-year overall survival was 75.6% [95%CI: 47.3%, 90.1%] for MRD-negative patients vs. 17.9% [95%CI: 4.4%, 38.8%] for those with residual disease (p < .001). Twelve subjects (34%) had known epigenetic alterations with 8 (67%) achieving a CR, 7 (88%) of whom were MRD negative. Correlative pharmacodynamics demonstrated the biologic activity of decitabine and vorinostat and identified specific gene enrichment signatures in nonresponding patients. Overall, this therapy was well-tolerated, biologically active, and effective in pediatric patients with R/R AML, particularly those with epigenetic alterations.
Brow Presentation
Authors: L. Bhose
Journal: BMJ (1961)

colorimetric determination of operative bleeding (Baronofsky et al., 1946).Moreover, sponge-weighing and constant-reference to the volume of blood in the suction bottles enables progress assessments of blood loss to be made and blood replacement to be geared accurately to the loss.Routine use of this method improves the surgeon's judgment of the volume of blood being lost.A better surgical technique is likely to be developed as a result of increased attention to measurement of the blood loss.Blood is a valuable commodity.Accurate measure- ment of blood loss leads to saving of blood for our community's blood banks.In some patients undergoing major operations the measured blood loss is small and transfusion is clearly unnecessary.With this simple method geriatric patients can usually be maintained at a normotensive level even during such radical surgery as aortic replacement.Survival rates show gratifying improvement.In view of its many advantages, this simple method should be a routine part of modern theatre practice.
Dependence on dextromoramide.
Authors: R. Seymour-Shove
Journal: BMJ (1967)

MEDICAL JOURNAgirth, but without signs of obstruction.Para- centesis revealed the above-mentioned findings.Laparotomy was undertaken and a gangrenous appendix was removed.It had obviously per- forated a considerable time before operation.The total duration of symptoms was three weeks.Complete recovery ensued.Case 3.-A 28-year-old Bantu male was admitted with a complaint of generalized weakness and increasing abdominal girth.Paracentesis produced a fluid of similar character to that obtained in the other two cases.At laparotomy a perforation of ileum was found approximately 4 ft.(1.2 m.) from the ileocaecal valve, the per- foration being partially walled off by descending colon and the resulting abscess cavity extending into the retroperitoneal space in the left flank.Resection and end-to-end anastomosis was per- formed.The clinical appearances suggested and pathological report confirmed that the condition was due to Crohn's disease.The patient died within 24 hours of operation.Thus of five cases presenting with ascites all were infective in origin, two being due to tuberculosis and three to peritonitis secon- dary to perforation of bowel.One tubercu- lous patient was submitted to laparotomy and the diagnosis made only after pathological report on a biopsy, the appearances suggest- ing carcinomatosis, and the other diagnosed as a result of a previous history of tuberculosis.Facilities for biochemical examinations are not available at this hospital.-Weare, etc.,
The future of adult cardiology. Council on Long Range Planning and Development in cooperation with the American College of Cardiology
Journal: JAMA (1989)

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
Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans
Authors: Jordi Mayneris-Perxachs, Anna Castells-Nobau, María Arnoriaga-Rodríguez, Josep Garre-Olmo, Josep Puig, Rafael Ramos, Francisco Martínez-Hernández, Aurelijus Burokas, Clàudia Coll, José Maria Moreno-Navarrete, Cristina Zapata-Tona, Salvador Pedraza, Vicente Pérez-Brocal, Lluís Ramió-Torrentà, Wifredo Ricart, Andrés Moya, Manuel Martínez-García, Rafael Maldonado, José-Manuel Fernández-Real
Journal: Cell Host & Microbe (2022)

Growing evidence implicates the gut microbiome in cognition. Viruses, the most abundant life entities on the planet, are a commonly overlooked component of the gut virome, dominated by the Caudovirales and Microviridae bacteriophages. Here, we show in a discovery (n = 114) and a validation cohort (n = 942) that subjects with increased Caudovirales and Siphoviridae levels in the gut microbiome had better performance in executive processes and verbal memory. Conversely, increased Microviridae levels were linked to a greater impairment in executive abilities. Microbiota transplantation from human donors with increased specific Caudovirales (>90% from the Siphoviridae family) levels led to increased scores in the novel object recognition test in mice and up-regulated memory-promoting immediate early genes in the prefrontal cortex. Supplementation of the Drosophila diet with the 936 group of lactococcal Siphoviridae bacteriophages resulted in increased memory scores and upregulation of memory-involved brain genes. Thus, bacteriophages warrant consideration as novel actors in the microbiome-brain axis.