tbuckley/cabot-search huggingface dataset:
Comparative ctDNA analyses of African-American and Caucasian patients with CRPC.
Authors: Ellen B. Jaeger, Sydney Caputo, William Fleming, Charlotte Manogue, Alex Lieberman, Isabelle P. Sussman, Patrick Miller, Malcolm Light, Minqi Huang, Pedro C. Barata, Brian E. Lewis, Jodi Lyn Layton, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2022)

24 Background: Somatic genetic analyses have indicated genetic distinctions in AA as compared to C patients. In the Mahal et al. study (1) evaluating a broad spectrum of pts with tissue based assays, FOXA1 mutations were more frequent in AA men and TP53 mutations were less frequent in AA men as compared to C men. In a separate analysis by Khashab et al. (2) conducted in prostate cancer pts receiving androgen deprivation therapy, using both tissue and ctDNA assays, the authors reported AR, TP53, SPOP, and BRCA2 were more frequently mutated in AA men as compared to C men. Herein we assessed the Guardant 360 platform in assessing ctDNA differences in AA and C men, all of whom had CRPC at the time assays were performed. Methods: Guardant 360 was used to analyze ctDNA with a cut-off of &gt;0.5% for allelic fractions for ascertaining the presence or absence of pathogenic mutations and various amplifications. Lower allelic fractions were not analyzed given these may represent less relevant mutations. Depending on the timing of the assays (2015-2021), 70-83 genes were analyzed. All pts had CRPC and all patients were treated at Tulane Cancer Center. Chi Square analyses were used to determine statistical differences. AR, BRCA2, and TP53 were assessed but SPOP and FOXA1 were not assessable in the Guardant ctDNA assay. Both mutations and amplifications were evaluated. Results: Among men with CRPC, a total of 48 AA men and 179 C men were analyzed using ctDNA. Clear distinctions were found in the alteration reported in APC, TP53, and CDK12. TP53 was less frequently mutated and other genes were more frequently altered in the AA men. Conclusions: Using Guardant ctDNA assays in men with CRPC, clear distinctions were found in AA men as compared to C men. It is unclear why these results differ from that reported by others, however distinctions in both the assays and the populations are notable.[Table: see text]
Congenital malformations.
Authors: E. Alberman
Journal: BMJ (1989)

patients the journey to hospital represents a major under- taking.To overcome these difficulties the Royal National Institute for the Deaf has proposed that a three month course should be set up to prepare workers to act as "hearing aid dispensers."They would record audiograms, take impressions of patients' ears so that an insert can be made, and finally issue the aid and counsel the patient in its use.The proposal is that these dispensers should work in the community visiting health centres and larger practices.Unfortunately the job description and the probable pay scale are hardly likely to attract applicants of calibre in sufficient numbers to meet the need.Another solution would be to enlist the help of practice nurses.They have already satisfied stringent educational requirements and have a scientific and medical background.They are experienced in dealing with accumulations of wax (so often a problem for wearers of hearing aids), otitis externa, and other ear problems.They are accustomed to advising and educating patients, and many record audiograms in the practice.With instruction, they could take a key part in dispensing hearing aids.Perhaps the best way forward would be to make hearing aids prescribable by general practitioners, subject to suitable regulations.Courses to update general practitioners in the
Age-related GSK3β overexpression drives podocyte senescence and glomerular aging
Authors: Yudong Fang, Bohan Chen, Zhangsuo Liu, Athena Y. Gong, William T. Gunning, Yan Ge, Deepak Malhotra, Amira F. Gohara, Lance D. Dworkin, Rujun Gong
Journal: Journal of Clinical Investigation (2022)

As life expectancy continues to increase, clinicians are challenged by age-related renal impairment that involves podocyte senescence and glomerulosclerosis. There is now compelling evidence that lithium has a potent antiaging activity that ameliorates brain aging and increases longevity in Drosophila and Caenorhabditis elegans. As the major molecular target of lithium action and a multitasking protein kinase recently implicated in a variety of renal diseases, glycogen synthase kinase 3β (GSK3β) is overexpressed and hyperactive with age in glomerular podocytes, correlating with functional and histological signs of kidney aging. Moreover, podocyte-specific ablation of GSK3β substantially attenuated podocyte senescence and glomerular aging in mice. Mechanistically, key mediators of senescence signaling, such as p16INK4A and p53, contain high numbers of GSK3β consensus motifs, physically interact with GSK3β, and act as its putative substrates. In addition, therapeutic targeting of GSK3β by microdose lithium later in life reduced senescence signaling and delayed kidney aging in mice. Furthermore, in psychiatric patients, lithium carbonate therapy inhibited GSK3β activity and mitigated senescence signaling in urinary exfoliated podocytes and was associated with preservation of kidney function. Thus, GSK3β appears to play a key role in podocyte senescence by modulating senescence signaling and may be an actionable senostatic target to delay kidney aging.
Abstract 365: Left Ventricular Wall Findings in Non-Electrocardiography-Gated Contrast-Enhanced Computed Tomography After Extracorporeal Cardiopulmonary Resuscitation
Authors: Kazuhiro Sugiyama, Kazuki Miyazaki, Takuto Ishida, Takahiro Tanabe, Yuichi Hamabe
Journal: Circulation (2018)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is a promising treatment for refractory cardiac arrest. Computed tomography (CT) is often performed after ECPR for diagnosis of etiology and evaluation of complications. However, few studies have reported left ventricular wall findings in contrast-enhanced CT (CE-CT) after ECPR. This study examined the left ventricular wall CE-CT findings after ECPR, and evaluated the association between these findings and the results of coronary angiography and prognosis. Method: We evaluated out-of-hospital cardiac arrest patients who were treated with ECPR and then underwent both non-ECG gated CE-CT and coronary angiography at our center between January 2011 and April 2018. The left ventricular wall CE-CT findings at 90 s after contrast injection were classified as follows: homogeneously-enhanced (HE), left ventricular wall was homogeneously enhanced; segmental defect (SD), left ventricular wall was not segmentally enhanced according to coronary artery territory; total defect (TD), entire left ventricular wall was not enhanced; and others. Significant stenosis on coronary angiography, survival to hospital discharge, and successful weaning from extracorporeal membrane oxygenation (ECMO) were examined. Results: A total of 111 patients were eligible. Median age was 59 years, and 85 (77%) had initial shockable rhythm. A total of 37 (33%) survived to hospital discharge. HE was observed in 33 patients, SD in 41, TD in 15, and others in 22. Among 74 patients who underwent CT prior to coronary angiography, SD predicted significant stenosis, with sensitivity of 83% and specificity of 100%. Among all patients, 28 (85%) with HE, 15 (37%) with SD, and 3 (20%) with TD were weaned successfully from ECMO. In addition, 17 (52%) patients with HE, 10 (24%) with SD, and 2 (13%) with TD survived to hospital discharge. Conclusion: SD could predict coronary artery stenosis with good specificity. Patients with HE had higher success rates for weaning from ECMO. On the other hand, TD was associated with poor outcomes. The left ventricular wall findings in non-ECG gated CE-CT after ECPR might be useful in diagnosis and prognostication.
ENCEPHALITIS
Authors: W. G. Wyllie
Journal: BMJ (1934)

The subject of encephalitis is specially suitable for the section of diseases of children because in so many of its forms it is the period of childhood which is principally affected.The term " encephalitis," however, must be interpreted in its broadest sense.It is used to cover a large and heterogeneous variety of conditions, some inflam- matory, others toxi-degenerative, and others of a vascular nature-embolic, haemorrhagic, and thrombotic.For the clinician it is often impossil?leto make a pathological diagnosis with any certainty, as the symptoms presented by the patient can only ind.cate which parts of the brain are involved, and may be produced by a variety of causes.In the first place, we recognize two main types of encephalitis-the suppurative and the non-suppurative.About the former, suppurative encephalitis -or cerebral abscess, it is sufficient to say that it is due to an invasion of the central nervous system by pyogenic organisms, an(d
Comment on Timing of Surgery For Patients With Rectal Cancers Not Responding to Preoperative Chemoradiation
Authors: Prudvi Raj, Swapnil Patel, Amar Prem
Journal: JAMA Surgery (2022)

To the Editor The study by Deidda et al1 highlighting the detrimental impact of delay in surgery after radiation therapy for rectal cancers is commendable, especially in the era of rapidly increasing evidence for total neoadjuvant therapy.
RIVER POLLUTION
Authors: H. M. Wilson
Journal: BMJ (1929)

THERt mlust he very few mnedical m11en1 who lhave niot at one timiie or anotlher had their attenitioii drawni to the pollute(l conidition of ouir rivers, but thiere are fewer still who can reiimeber thie foulliess of some of the streams in our industrial areas thirtv or forty year-s ago, when little had been done to cheek their pollution.To give some picture of the coniditions of the streamiis at that timo, I cannot do better than repeat the often quLoted paragraph in the report, of the Roval Commiiiiission of 1865 (pages x and xi):The Rivers Aire and Calder tllrougliouit tlheir whole course are abused, obstructed, and polluted (to an extent scarcely conceivable by other tlhan eye-witnesses) from Skipton on the Aire, from Todmorden oni the Calder down to Castleford.The Rivers Aire and Calder, and their tributaries, are abused by passing into them huindreds of thousands of tons per annum of ashes, slag, and cinders from steam-boiler furnaces, ironworks, and domestic fires; by their being made a receptacle to a vast extent of broken pottery and worn-out utensils of metal, refuse brick from brick- yards and old buildings, earth, stone, and clay from quarries and excavations, road scrapings, street sweepings, etc.; by spent dyewoods and other solids used in the treatment of worsteds and woollens; by hundreds of carcasses of animals, as dogs, cats, pigs, etc., which are allowed to float on the surface of the streams or putrefy on their banks; and by the flowing in, to the amount of very 'many million gallons per day, of water poisoned, cor- rupted, and clogged by refuse from mines, chemical works, dyeing, scouring, and fulling worsted and woollen stuffs, skin cleaning and tanning, slaughterhouse garbage, and the sewage of towns and liouses."This description of the Rivers Aire and Calder may be said to apply, with more or less accuracy, to many of the streams in the industrial areas, particularly in Yorkshire anid Lancashire.
Control and prevention of tuberculosis in Britain: an updated code of practice. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society.
Authors: Craig Skinner
Journal: BMJ (1990)

A subcommitte was appointed by the Joint Tuberculosis Committee of the British Thoracic Society to review and bring up to date guidelines on control measures for tuberculosis. The updated code of practice emphasises that all cases of tuberculosis must be notified. A minority of patients need admission, and those with positive sputum smears should be regarded as infectious until they have received two weeks of chemotherapy. NHS staff at risk should be protected, and evidence of infectious tuberculosis should be sought as routine among certain prospective NHS employees, schoolteachers, and others. Contact tracing should be vigorously pursued, and all entrants to Britain from countries where tuberculosis is common should be screened. BCG vaccination should be offered in selected instances, and local organisation of tuberculosis services should be extended.
Virtual genetics board for enhancing knowledge and practice of prostate cancer genetic testing: The ENGAGEMENT study.
Authors: Veda N. Giri, Laura Gross, Heather H. Cheng, Jessica Russo, Channing Judith Paller, Jennifer M Johnson, Emily Steinberger Weg, Stacy Loeb
Journal: Journal of Clinical Oncology (2022)

184 Background: With the increasing indications for germline testing for prostate cancer (PCA), there is a growing need for a spectrum of providers to develop working knowledge and understand considerations of germline testing and genetic counseling. A virtual genetics board was developed to provide case-based discussion of PCA germline testing, standard of care and clinical trial management, hereditary cancer management, and genetic counseling. Methods: A virtual genetics board was launched including experts in GU medical oncology, prostate cancer genetics, radiation oncology, urology, clinical trials, genetic counseling, and molecular oncology. Conferences are held monthly, with cases covering metastatic PCA, high-risk disease, early-stage PCA, or PCA screening. Participants complete a baseline survey of demographic information and cancer genetics knowledge. Post-conference survey includes retaking knowledge questions and feedback on cases and Zoom format. Results: At the time of this report, 57 participants have engaged in the virtual genetics board. Participants include genetic counselors (21%), nurse practitioners (21%), medical oncologists (14%), researchers/scientists (14%), nurses (9%), urologists (5%), radiation oncologists (4%), and other specialties. Practice settings include academic centers (49%), public hospitals (16%), private hospitals (11%), and other settings. The baseline survey was completed by 55 participants, and post-conference survey by 34 participants. Knowledge scores increased regarding cancer inheritance, rates of mutations in metastatic PCA, BRCA2-related cancers, risk of PCA for HOXB13 carriers, and risk for PCA in African American males. Feedback was positive, with over 90% favorable responses on usability of technology, usefulness of case discussions, and relevance to informational needs. Conclusions: Initial results support a virtual genetics board to increase PCA genetic evaluation knowledge. The ENGAGEMENT study is ongoing with monthly live case discussions that are also recorded for on-demand viewing; registration is available at www.prostategenetics.com/engagement.[Table: see text]
THE "HERB KING" GONE WRONG.
Journal: JAMA (1903)

An irregular practitioner calling himself the "herb king" was recently arrested in a California town for practicing without a license, and inaugurated a not uncommon but peculiar defense. He had a number of his patrons, or those who signed as such, many of them of the sympathetic softer sex, publish a card in the local paper saying that they had received benefit from his treatment when regular physicians had failed to relieve them, and that some of the signers owed their lives to his skill. They recommended his medicines, and alleged that his prosecution was wholly unwarranted. The sequel came a few days later, when he was again arrested and held in heavy bail for a criminal assault on one of his female patients, whether or not one of the signers or only one duped by their recommendation the record does not state. Such are the ways of the quack.
Massachusetts Medical Society
Authors: Fritz B. Talbot
Journal: New England Journal of Medicine (1965)

Fritz Bradley Talbot died on October 31, 1964, in his eighty-sixth year. He graduated from Harvard College with the Class of 1900, and from Harvard Medical School in 1905. After completing a medical internship at the Massachusetts General Hospital, he began practice in Boston, and thereafter devoted himself to the study and care of diseases of infants and children.Working with Dr. John Lovett Morse and others, he helped to spread the gospel of clean milk and hygienic dairies, which eventually led to the compulsory pasteurization of milk in Massachusetts. He established the "Wet Nurse" Directory, the first in America, . . .
Glomangioma
Authors: A. C. Lendrum, W. A. Mackey
Journal: BMJ (1939)

<h3>Objective</h3> To measure health-related quality of life (HRQoL) and well-being in older people with end-stage kidney disease (ESKD) and to determine the association between treatment type and sociodemographic characteristics on these outcome measures. In addition, to assess the convergent validity between the HRQoL and well-being measure and their feasibility and acceptability in this population. <h3>Design</h3> Prospective cross-sectional study. <h3>Setting</h3> Three renal units in the UK and Australia. <h3>Participants</h3> 129 patients with ESKD managed with dialysis or with an estimated glomerular filtration ≤10 mL/min/1.73 m<sup>2</sup> and managed with comprehensive conservative, non-dialytic care. <h3>Outcome measures</h3> HRQoL and well-being were assessed using Short-Form six dimensions (SF-6D, 0–1 scale); Kidney Disease Quality of Life (KDQOL-36) (0–100 scale) and Investigating Choice Experiments Capability Measure-Older people (ICECAP-O, 0–1 scale). Linear regression assessed associations between treatment, HRQoL and well-being. Pearson’s correlation coefficient assessed convergent validity between instruments. <h3>Results</h3> Median age of 81 years (IQR 78–85), 65% males; 83 (64%) were managed with dialysis and 46 (36%) with conservative care. When adjusted for treatment type and sociodemographic variables, those managed on dialysis reported lower mean SF-6D utility (−0.05, 95% CI −0.12 to 0.01); lower KDQOL Physical Component Summary score (−3.17, 95% CI −7.61 to 1.27); lower Mental Component Summary score (−2.41, 95% CI −7.66 to 2.84); lower quality of life due to burden (−28.59, 95% CI −41.77 to −15.42); symptoms (−5.93, 95% CI −14.61 to 2.73) and effects of kidney disease (−16.49, 95% CI −25.98 to −6.99) and lower overall ICECAP-O well-being (−0.07, 95% CI −0.16 to 0.02) than those managed conservatively. Correlation between ICECAP-O well-being and SF-6D utility scores was strong overall, 0.65 (p&lt;0.001), but weak to moderate at domain level. <h3>Conclusions</h3> Older people on dialysis report significantly higher burden and effects of kidney disease than those on conservative care. Lower HRQoL and well-being may be associated with dialysis treatment and should inform shared decision-making about treatment options. <h3>Trial registration number</h3> UK (IRAS project ID: 134360andREC reference 14/LO/0291) and Australia (R20140203 HREC/14/RAH/36).
A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization
Authors: Tingting Yang, Yuzhu Hu, Junming Miao, Jing Chen, Jiagang Liu, Yongzhong Cheng, Xiang Gao
Journal: Acta Pharmaceutica Sinica B (2022)

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.
Kallmann Syndrome
Authors: Elena I. Rugarli
Journal: JAMA (1993)

IN THE last few years, numerous discoveries in the field of human genetics have had a significant impact both on medical practice and on basic science. Kallmann syndrome represents the first human disease caused by a neuronal migration defect for which the gene has been identified and is a good example of how genetics has permitted the integration of clinical observation with developmental biology, contributing to the understanding of disease pathogenesis. The purpose of this article is to review the clinical, biological, and molecular genetic aspects of Kallmann syndrome and to discuss their correlation. <h3>CLINICAL FEATURES AND PATHOGENESIS</h3> Kallmann syndrome is an inherited disorder, defined by the association of hypogonadism and anosmia. Since the description of the first patients by Kallmann in 1944, many familial and sporadic cases have been reported.<sup>1-3</sup>Autosomal dominant, autosomal recessive, and X-linked recessive inheritance patterns have been described, indicating genetic heterogeneity.<sup>2,3</sup>The incidence of
Staffing of accident and emergency departments.
Authors: W Windebank, F Moran
Journal: BMJ (1973)

thromboembolism.Four of these patients had normal pulmonary "wedged" pressures (indirect left atrial pressures) and in one there was a slight increase.In the remaining six patients the pulmonary "wedged" pressure record could not be analysed because of difficulty in identifying an appropriate wave form.This could have been due to technical imperfection, but an alternative explanati might be pulmonary venous hypertension without left atrial hypertension.The occurrence of pulmonary venous con- striction following experimental pulmonary embolism was demonstrated by Daicoff et al.S This mechanism could account for pulmonary oedema in the absence of left heart failure and might also account for the difficulty in obtaining an adequate pulmonary "wedged" record.Although in man the mechanism is obscure, there is no doubt that pulmonary oedema can occur as a result of pulmonary thromboembolism.-Weare, etc.,