tbuckley/cabot-search huggingface dataset:
Phase 2 trial of immunotherapy in tumors with CDK12 inactivation (IMPACT): Results from cohort A of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) receiving dual immune checkpoint inhibition (ICI).
Authors: Ajjai Shivaram Alva, Jinju Li, Jonathan Chou, Melissa Andrea Reimers, Rana R. McKay, Jingsong Zhang, Stephanie Daignault-Newton, Phillip Lee Palmbos, Zachery R Reichert, Marcin Cieslik, Arul Chinnaiyan, Wassim Abida
Journal: Journal of Clinical Oncology (2022)

103 Background: Prostate cancer with CDK12 inactivation represents a distinct subtype in mCRPC, tumors are characterized by excessive tandem duplications, genomic instability, gene fusion-caused putative neoantigens and increased tumor T cell infiltration. Retrospective experiences with ICI in CDK12 inactivation CRPC pts reported PSA and radiographic responses. We conducted a prospective multi-site clinical trial of ipilimumab and nivolumab in CDK12 inactivation or mutated cancers. Herein, we report our findings in the completed cohort A of men with mCPRC. Methods: Eligible pts had mCRPC (ongoing androgen deprivation therapy with serum testosterone £ 50 ng/dL) and putative CDK12 inactivation of function aberrations on any commercial or institutional CLIA/CAP approved next generation sequencing assay. Archival tumor tissue was requested for correlative biomarker analysis. Pts received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV q3 weeks for up to 4 cycles, followed by maintenance nivolumab at 480 mg IV q4 weeks until disease progression, intolerable toxicity, or consent withdrawal. The primary endpoint was PSA response, defined as a greater than or equal to 50% decline in PSA from baseline. Secondary endpoints included safety/toxicity, secondary efficacy measures including QoL and overall survival. Exploratory objectives included baseline tumor whole exome analysis and changes in circulating immune profiles with therapy. Results: As of data cut-off in Aug 2021, 28 mCRPC pts enrolled in Cohort A; median ECOG PS was 1 (0-2 range), 22/28 had Gleason 8-10 cancer, mean baseline PSA at study entry was 231 ng/dL, all pts had received ≥1 prior oral androgen signaling inhibitor and ≥1 cytotoxic chemotherapy. Unconfirmed PSA ≥30% decline was seen in 6/28 pts (21.4%) and PSA ≥50% decline in 4/28 pts (14.2%). Grade ≥3 possible/probable/definite adverse events were noted in 7/28 (25%) and SAEs in 10/28 pts (35.7%). Six pts (21.4%) experienced a rapid PSA increase by ≥ 10-fold over baseline. Conclusions: Combination immunotherapy was reasonably tolerated in this heavily pre-treated population and was associated with unconfirmed PSA responses in a subset of pts. Ongoing correlative analyses could explain responses mechanistically. Enrollment in Cohort B of non-prostate cancers and Cohort C of nivolumab monotherapy in prostate cancer are still ongoing. Clinical trial information: NCT03570619.
Tuberculosis and response to cancer chemotherapy
Authors: E. M. Greenspan
Journal: JAMA (1979)

<h3>To the Editor.—</h3> We would like to comment in general on the use of indices of obesity—specifically about using the ponderal index (PI), as suggested by Flewellen and Bee (241:884, 1979). These investigators correctly state that the medical community has not adopted a commonly used method of quantifying obesity. However, we suggest that this is not due to any lack of evidence in the literature regarding relative usefulness of obesity indices. Such information is available. Billewicz et al<sup>1</sup>offered the following criteria for a good index: (1) maximum correlation with adiposity, (2) minimum correlation with height, and (3) ease of computation. Using these criteria, Billewicz and colleagues compared PI, weight-to-height ratio (W/H), and body mass index (BMI). Each can be defined as follows: PI=height/[unk] weight; W/H= weight/height; and BMI=weight/ (height)<sup>2</sup>. The BMI correlated maximally with adiposity and minimally with height, whereas PI displayed least correlation with adiposity and
Comparative analysis of antibody- and lipid-based multiplexing methods for single-cell RNA-seq
Authors: Viacheslav Mylka, Irina Matetovici, Suresh Poovathingal, Jeroen Aerts, Niels Vandamme, Ruth Seurinck, Kevin Verstaen, Gert Hulselmans, Silvie Van den Hoecke, Isabelle Scheyltjens, Kiavash Movahedi, Hans Wils, Joke Reumers, Jeroen Van Houdt, Stein Aerts, Yvan Saeys
Journal: Genome biology (2022)

Abstract Background Multiplexing of samples in single-cell RNA-seq studies allows a significant reduction of the experimental costs, straightforward identification of doublets, increased cell throughput, and reduction of sample-specific batch effects. Recently published multiplexing techniques using oligo-conjugated antibodies or -lipids allow barcoding sample-specific cells, a process called “hashing.” Results Here, we compare the hashing performance of TotalSeq-A and -C antibodies, custom synthesized lipids and MULTI-seq lipid hashes in four cell lines, both for single-cell RNA-seq and single-nucleus RNA-seq. We also compare TotalSeq-B antibodies with CellPlex reagents (10x Genomics) on human PBMCs and TotalSeq-B with different lipids on primary mouse tissues. Hashing efficiency was evaluated using the intrinsic genetic variation of the cell lines and mouse strains. Antibody hashing was further evaluated on clinical samples using PBMCs from healthy and SARS-CoV-2 infected patients, where we demonstrate a more affordable approach for large single-cell sequencing clinical studies, while simultaneously reducing batch effects. Conclusions Benchmarking of different hashing strategies and computational pipelines indicates that correct demultiplexing can be achieved with both lipid- and antibody-hashed human cells and nuclei, with MULTISeqDemux as the preferred demultiplexing function and antibody-based hashing as the most efficient protocol on cells. On nuclei datasets, lipid hashing delivers the best results. Lipid hashing also outperforms antibodies on cells isolated from mouse brain. However, antibodies demonstrate better results on tissues like spleen or lung.
Abstract 286: Chance of Bystander Defibrillation According to Number of Nearby Automated External Defibrillators in Out-Of-Hospital Cardiac Arrests
Authors: Lena Karlsson, Christopher Sun, Carolina Malta Hansen, Mads Wissenberg, Freddy Lippert, Christian Torp-Pedersen, Timothy Chan, Fredrik Folke
Journal: Circulation (2018)

Introduction: Use of automated external defibrillators (AEDs) for early defibrillation in out-of-hospital cardiac arrest (OHCA) substantially increases chance of survival. Aim: To examine the relationship between number of nearby accessible AEDs and chance of bystander defibrillation. Methods: All OHCAs (2008-2016), and all publicly available AEDs (2007-2016) in Copenhagen were identified. The route distances between OHCAs and AEDs were calculated to determine the number of accessible AEDs ≤100m of an OHCA (OHCA coverage). Multiple logistic regression was performed to identify the adjusted Odds Ratios (ORs) of OHCA characteristics, including the number of AEDs covering an OHCA, on bystander defibrillation. The regression model was evaluated using receiver operator characteristics (ROC). Multiple logistic regression was also used to determine the predicted probability (through a 2000 iteration bootstrap approach) of bystander defibrillation for public vs. residential OHCAs, according to the number of accessible AEDs covering the OHCA, defined as covered by 0, 1 or &gt;1 AED. Results: There were 1830 AEDs registered in Copenhagen. Of 2500 OHCAs, 75.2% (n=1879) occurred in residential locations of which 98.1% were not covered by an AED, 1.7% were covered by 1 AED only, and 0.2% were covered by &gt;1 AED. The corresponding figures for public OHCAs (n=621, 24.8%) were 87.5%, 9.0%, and 3.5%, respectively. Overall, the number of accessible AEDs covering the OHCA, public location, bystander witnessed arrest and bystander CPR were significantly associated with bystander defibrillation (OR (95%CI): 1.75 (1.24-2.46); 4.25 (2.75-6.57); 3.12 (1.84-5.27); 2.33 (1.44-3.75), respectively. (ROC=82%)). The predicted probability of bystander defibrillation for public OHCAs was 12.2% (95%CI: 9.5-14.9) with no AED covering the OHCA, 24.7% (95%CI: 18.2-31.3) with 1 AED, and 39.8% (95%CI: 23.4-56.7) with &gt;1 AED. The corresponding figures for residential OHCAs were 2.1% (95%CI: 1.5-2.8), 4.3% (95%CI: 2.5-6.8), and 4.0% (95%CI: 0.9-10.8), respectively. Conclusions: Rates of bystander defibrillation significantly improved with increasing number of accessible AEDs covering the OHCA, especially for public OHCAs.
Operative Cholangiography
Authors: E. S. R. Hughes, R. H. Kernutt
Journal: BMJ (1954)

CONGENITAL GALACTOSAEMIA BmDIT=U is supported by the observations of Topper and Stetten (1951), who fied D-galactose-l-C" to rats and recovered glycogen from the liver which, on hydrolysis, yielded glu- cose having 90% of its isotope content in position 1.Thus inhibition or lack of any of the enzyme systems involved in reactions A or B would appear a possible lesion in these children.That disease may arise from such a lack of a specific enzyme system has been elegantly established by Cori and Cori (1952), who demonstrated lack of glucose-6- phosphatase activity in liver homogenates from certain cases of glycogen storage disease.Alternatively the galactosaemia could arise as a result of hepatic damage, following immunization.The galactosetolerance tests would offer no help in differentiating this secondary defect and the primary defect mentioned above.Bessis (1947) demonstrated profound histological changes in the liver in cases of fatal icterus gravis, but Gerrard (1952) could detect no significant residual hepatic damage in cases surviving Rh sensitization.Gorter (1951) reported galacto- suria occurring in association with A-O blood group incom- patibility, and in the mother of the present case an anti-A agglutinin was detected.However, Townsend et al. (1951), reviewing the relationship between galactosuria and Laen- nec's cirrhosis, concluded that the defect of galactose metabolism was primary and that the cirrhosis was secondary.This conclusion is supported by the normal liver-function tests in our case.Bray et al. (1952) detected an excess aminoaciduria in two of their cases, but no observations were recorded on the blood amino-acid nitrogen.We were unable to detect this urinary abnormality on two separate occasions.Such an aminoaciduria might result either from liver damage or from renal tubular deficiency.It is noteworthy that the initial biochemical findings in our case resembled those of infantile renal acidosis.Latner and Burnard (1950) have ascribed this condition to failure of the proximal renal tubule to reabsorb bicarbonate ions.It is conceivable that both these tubular lesions causing excess aminoaciduria and failure of bicarbonate resorption have arisen as toxic manifestations of the galactosaemia, but it must be admitted that we need to study many more such cases before any final conclusion can be reached, and that the association of the acidosis and galactosaemia may be fortuitous.SummaryThe clinical and pathological findings and response to treatment of a case of galactosaemia associated with hyperchloraemic renal acidosis and haemolytic disease of the newborn is described.It is thought that galactosaemia arises as a congenital condition due to a specific lack of enzymes involved in the metabolism of galactose.The possibility that the renal acidosis arose as a result of the toxic effect of galactose on the renal tubules is considered.We are indebted to Dr. I. M. Anderson, whose case this was, and Professor N. F
Prostate-specific antigen (PSA) outcomes in black (B) and white (W) chemotherapy-naïve (CN) prostate cancer (PC) patients (pts) treated with enzalutamide (ENZA).
Authors: Alicia K. Morgans, Agnes Hong, Sharanya Murty, Nader N. El-Chaar, Krishnan Ramaswamy, Anna D. Coutinho, David Nimke, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2022)

20 Background: Population-level data suggest that B men are more likely to be diagnosed and die from PC. In juxtaposition, across multiple treatments for advanced PC, studies suggest B men have better survival than W men, including with novel hormone therapies (NHTs) such as ENZA. Whether improved survival is driven by better clinical response is unknown as data on racial differences in treatment response for ENZA are limited. This study assessed real-world PSA outcomes (response and progression) of ENZA-treated B vs W CN PC pts in the US. Methods: This retrospective cohort study included PC pts who initiated ENZA in the IntrinsiQ Specialty Solutions urology electronic medical records database from Sept 1, 2014 to Feb 28, 2018. The index date was the first prescription for ENZA. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. Baseline characteristics, PSA response (PSA decline ≥50% or ≥90%), and clinical progression-free survival (cPFS) were assessed by race. Kaplan-Meier and Cox models adjusting for baseline characteristics were used to estimate PSA response and cPFS. Results: The study included 214 B and 1,332 W CN PC pts. Black pts were younger and had a higher baseline median PSA than W pts. Charlson Comorbidity Index (CCI), median duration of therapy, follow-up time, and number of post-index PSA tests were similar between races. In adjusted analyses, the chances of pts achieving ≥50% PSA decline was similar, whereas a numerically higher trend was observed for ≥90% PSA decline in B pts (Table). In addition, B men had significantly better cPFS (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.68, 0.98; p=0.03) [Table]. Conclusions: This real-world study found similar PSA response in B and W CN PC pts treated with ENZA but suggests that B pts may have better cPFS than W pts. Further research is warranted to validate these findings.[Table: see text]
Defining hereditary upper tract urothelial carcinoma: Implications for genetic testing and clinical management.
Authors: Hong Truong, Rania Sheikh, Yelena Kemel, Manuel De Jesus Escano, Aliya Khurram, Peter Reisz, Andrew Thomas Lenis, Alvin C. Goh, Eugene K. Cha, Bernard H. Bochner, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, David B. Solit, Zsofia Kinga Stadler, Alicia Latham, Kenneth Offit, Maria Isabel Carlo, Jonathan Coleman, Hikmat A. Al-Ahmadie
Journal: Journal of Clinical Oncology (2022)

523 Background: Despite being a rare cancer, upper tract urothelial carcinoma (UTUC) is the third most common core cancer associated with Lynch syndrome (LS) after colorectal and endometrial cancers. Yet, there is no established guideline to identify patients with UTUC who are at risk of carrying germline mutations in LS-associated genes. The objective of this study is to define selection criteria for patients with UTUC for LS screening. Methods: We retrospectively identified patients with UTUC who underwent germline sequencing of ≥77 cancer susceptibility genes using next generation sequencing (NGS) as part of a prospective matched tumor-normal genomic profiling initiative from 04/2015 to 04/2021. Mismatch repair protein status was evaluated by immunohistochemical (IHC) staining for MMR genes MSH2, MSH6, MLH1, and PMS2. Microsatellite instability (MSI) status was determined using NGS. Diagnostic performance of clinical and tumor-based screening criteria was assessed by the presence of germline pathogenic/likely pathogenic variants (PGVs) in MMR genes. Results: A total of 232 patients with UTUC underwent germline testing; median age of diagnosis was 67 years (interquartile range 59 – 73). Of these patients, 70% were male, 43% had UTUC diagnosed before the age of 65, 85% had high grade UTUC,12% had bilateral UTUC, 11% had metastasis at diagnosis, 10% and 31% had personal and family history of LS-associated cancers, respectively. PGVs in moderate or high-penetrance genes were identified in 31 (13%) patients including 6 (3%) in BRCA1/ 2 and 21 (9%) in MMR genes (13 MSH2, 4 MSH6, 4 MLH1). A total of 10/21 (48%) patients with MMR PGVs developed UTUC as their first cancer diagnosis. Of patients with MMR PVGs, 15/16 (94%) had MMR-deficient tumors and 12/18 (67%) had MSI-high tumors. Personal and family history of LS core cancers (p &lt; 0.001), age of diagnosis &lt; 65 (p = 0.008), MSI-high (p &lt; 0.001), and MMR-deficiency (p &lt; 0.001) were associated with MMR carrier status. Female gender (p = 0.7), HG UTUC (p = 0.5), and bilateral UTUC (p = 0.7) were not associated with MMR PGVs. Current NCCN genetic referral criteria for Lynch syndrome has high specificity in identifying patients with LS (100%) but missed 11/21 (52%) patients with UTUC and MMR PGVs. Conclusions: Current genetic referral guidelines for Lynch syndrome may miss a significant portion of patients with LS-associated UTUC. UTUC tumor should be investigated for MMR protein and MSI status with IHC or next generation sequencing methods to augment LS-screening of patients with UTUC and inform systemic treatment selection.
Diagnosing malnutrition.
Authors: R Dionigi, L Dominioni, V Jemos, R Cremaschi, R Monico
Journal: Gut (1986)

The measurement of selected anthropometric, biochemical and immunological variables, and clinical judgment can be used to assess nutritional state. Nutritional assessment has three main aims: to define the type and severity of malnutrition; to identify high risk patients; to monitor the efficacy of nutritional support. The problems associated with the various methods to assess the nutritional state and the applications of nutritional assessment in clinical practice are presented and discussed.
PDTM-44. RADIATION DNA DAMAGE REPAIR INHIBITION BY GSK-J4 INDUCED CHROMATIN COMPACTION IN DIPG
Authors: Nundia Louis, Xingyao He, Andrea Piunti, Marc Morgan, Dusten Unruh, Amanda Saratsis, Rishi Lulla, Jason R Fangusaro, Craig Horbinski, Stewart Goldman, C David James, Ali Shilatifard, Rintaro Hashizume
Journal: Neuro-Oncology (2017)

Fractionated focal radiation therapy remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all children who suffer from this inoperable and uniformly fatal cancer show evidence of disease progression within months of completing radiation therapy, especially those who harbor the H3.3K27M mutation. Since chemotherapy does not provide any significant outcome improvement, it is crucial to find a suitable radiosensitizer. Our research has shown that the JMJD3 demethylase inhibitor, GSK-J4 exerts potent anti-tumor activity on H3K27M mutant DIPG cells, restores H3K27 methylation and decreases genes that encode proteins involved in DNA double-strand break (DSB) repair. We hypothesized that GSK-J4 may inhibit radiation-induced DNA repair via chromatin modification, making it a potential radiosensitizing agent. DNA damage repair was evaluated by quantitative PCR for DNA DSB repair genes and immunocytochemistry of DSB markers γH2AX and 53BP1. MNase digestion was used to analyze nucleosome assembly in cellular chromatin. Western blot was performed to assess DNA DSB repair protein expression. DNA repair assay and clonogenic survival assays are being conducted to assess DIPG response to RT + GSK-J4 combination therapy. In vivo response to GSK-J4 and radiation as monotherapies and in combination was measured by bioluminescence image and animal survivals. qPCR results showed that GSK-J4 significantly reduces DNA DSB repair genes such as PARP1, PARP2, SMARCB1 and BRCA1, in irradiated DIPG cells. Immunocytochemistry results support that GSK-J4 sustains high levels of γH2AX and 53BP1 in irradiated DIPG cells. MNase assay indicated that GSK-J4 causes chromatin compaction which prevents DNA DSB repair. Western blot showed sustained levels of γH2AX in irradiated DIPG cells treated with GSKJ4. Animal survival studies showed increased survival in mice undergoing combination treatment compared to radiation monotherapy. Results from DNA repair assay and clonogenic survival assays will be reported at the meeting.
EXPERIMENTS ON THE RÔLE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE
Authors: James B. Murphy, Ernest Sturm
Journal: The Journal of Experimental Medicine (1919)

Mice with high lymphocyte counts and increased activity of the lymphoid tissue induced by one exposure to intense dry heat exhibit a marked increase in the resistance to large doses of bovine tubercle bacilli as compared with that shown by control animals given a similar inoculation. This resistance, judged by the time of survival after inoculation, is increased from two- to threefold. The average length of life after inoculation for three groups of heated mice was 88, 69, and 67 days respectively, while the control groups averaged 16, 29, and 28 days respectively.
ARE THERE PSEUDODIPHTHERIA BACILLI VIRULENT FOR MAN?
Journal: JAMA (1904)

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
Angioimmunoblastic lymphadenopathy.
Authors: P Emery, G S Panayi
Journal: Annals of the Rheumatic Diseases (1988)

Angioimmunoblastic lymphadenopathySIR, We were interested to read the case report fromMcHugh et al.' We have been following up a patient who presented with similar clinical features, but in whom the findings of T lymphocyte subset analysis of synovial fluid (SF) and peripheral blood (PB) were contrasting (Table 1).
THE SYMPTOMATIC TREATMENT OF PNEUMONIA
Journal: JAMA (1921)

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