tbuckley/cabot-search huggingface dataset:
Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19
Authors: Yunlong Ma, Fei Qiu, Chunyu Deng, Jingjing Li, Yukuan Huang, Zeyi Wu, Yijun Zhou, Yaru Zhang, Yichun Xiong, Yinghao Yao, Yigang Zhong, Jia Qu, Jianzhong Su
Journal: Genome Medicine (2022)

Understanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.We constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N = 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells.We found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were highly expressed in these three cell types, respectively. CCR1+CD16+monocytes and ABO+ megakaryocytes with significantly up-regulated genes, including S100A12, S100A8, S100A9, and IFITM1, confer higher risk to the dysregulated immune response among severe patients. CXCR6+ memory CD8+ T cells exhibit a notable polyfunctionality including elevation of proliferation, migration, and chemotaxis. Moreover, we observed an increase in cell-cell interactions of both CCR1+ CD16+monocytes and CXCR6+ memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues. The enhanced interactions of CXCR6+ memory CD8+T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+T cell-mediated immunity against COVID-19 infection.We uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
Reduced COVID-19 Vaccine Response in Patients Treated with Biologic Therapies for Asthma
Authors: Martin C. Runnstrom, Andrea Morrison-Porter, Mayuran Ravindran, Hannah Quehl, Richard P. Ramonell, Matthew Woodruff, Rahulkumar Patel, Caroline Kim, Natalie S. Haddad, F. Eun-Hyung Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
The Effect of Geometry and TGF‐<i>β</i> Signaling on Tumor Cell Migration from Free‐Standing Microtissues
Authors: Jing Xie, Xinyu Hu, Lina Chen, Aigars Piruska, Zijian Zheng, Min Bao, Wilhelm T. S. Huck
Journal: Advanced Healthcare Materials (2022)

Recapitulation of 3D multicellular tissues in vitro is of great interest to the field of tumor biology to study the integrated effect of local biochemical and biophysical signals on tumor cell migration and invasion. However, most microengineered tissues and spheroids are unable to recapitulate in vitro the complexities of 3D geometries found in vivo. Here, lithographically defined degradable alginate microniches are presented to produce free-standing tumor microtissues, with precisely controlled geometry, high viability, and allowing for high cell proliferation. The role of microtissue geometry and TGF-β signaling in tumor cell migration is further investigated. TGF-β is found to induce the expression of p-myosin II, vimentin, and YAP/TAZ nuclear localization at the periphery of the microtissue, where enhanced nuclear stiffness and orientation are also observed. Upon embedding in a collagen matrix, microtissues treated with TGF-β maintain their geometric integrity, possibly due to the higher cell tension observed around the periphery. In contrast, cells in microtissues not treated with TGF-β are highly mobile and invade the surrounding matrix rapidly, with the initial migration strongly dependent on the local geometry. The microtissues presented here are promising model systems for studying the influence of biophysical properties and soluble factors on tumor cell migration.
Aberrant inflammatory responses to type I interferon in STAT2 or IRF9 deficiency
Authors: Florian Gothe, Jarmila Stremenova Spegarova, Catherine F. Hatton, Helen Griffin, Thomas Sargent, Sally A. Cowley, William James, Anna Roppelt, Anna Shcherbina, Fabian Hauck, Hugh T. Reyburn, Christopher J.A. Duncan, Sophie Hambleton
Journal: Journal of Allergy and Clinical Immunology (2022)

<h3>Background</h3> Inflammatory phenomena such as hyperinflammation or hemophagocytic lymphohistiocytosis are a frequent yet paradoxical accompaniment to virus susceptibility in patients with impairment of type I interferon (IFN-I) signaling caused by deficiency of signal transducer and activator of transcription 2 (STAT2) or IFN regulatory factor 9 (IRF9). <h3>Objective</h3> We hypothesized that altered and/or prolonged IFN-I signaling contributes to inflammatory complications in these patients. <h3>Methods</h3> We explored the signaling kinetics and residual transcriptional responses of IFN-stimulated primary cells from individuals with complete loss of one of STAT1, STAT2, or IRF9 as well as gene-edited induced pluripotent stem cell–derived macrophages. <h3>Results</h3> Deficiency of any IFN-stimulated gene factor 3 component suppressed but did not abrogate IFN-I receptor signaling, which was abnormally prolonged, in keeping with insufficient induction of negative regulators such as ubiquitin-specific peptidase 18 (USP18). In cells lacking either STAT2 or IRF9, this late transcriptional response to IFN-α2b mimicked the effect of IFN-γ. <h3>Conclusion</h3> Our data suggest a model wherein the failure of negative feedback of IFN-I signaling in STAT2 and IRF9 deficiency leads to immune dysregulation. Aberrant IFN-α receptor signaling in STAT2- and IRF9-deficient cells switches the transcriptional output to a prolonged, IFN-γ–like response and likely contributes to clinically overt inflammation in these individuals.
Reduction of residual tumors by photodynamic diagnosis-assisted TURBT using 5-aminolevulinic acid for high-risk nonmuscle-invasive bladder cancer (BRIGHT study).
Authors: Taketo Kawai, Haruki Kume, Keiji Inoue, Kiyohide Fujimoto, Masafumi Oyama, Hideaki Miyake, Haruhito Azuma, Hiroyuki Nishiyama, Nobuo Shinohara, Chikara Ohyama, Takahiko Mitsui, Atsushi Mizokami, Mutsushi Kawakita, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2022)

489 Background: High-risk non-muscle invasive bladder cancer (NMIBC) has high tumor residual rate of 40–60% after TURBT, and second TUR is strongly recommended. Photodynamic diagnosis-assisted TURBT (PDD-TURBT) using 5-aminolevulinic acid (5-ALA) has been reported to reduce residual tumors and intravesical recurrence. The purpose of this study is to investigate the residual tumor-reducing effect of PDD-TURBT for high-risk NMIBC and to explore the possibility that second TUR could be omitted by PDD-TURBT. Methods: We conducted an investigator-initiated multicenter prospective observational study (BRIGHT study; UMIN000035712) involving patients who underwent PDD-TURBT using 5-ALA and second TUR for high-risk NMIBC (high-grade UC or pT1 or concurrent CIS). The primary endpoint was tumor residual rate and the secondary endpoint was recurrence-free survival, which were compared with historical data (conventional TURBT) using propensity score-matching (PSM; caliper: 0.2). Assuming that the difference between the two groups was 20%, the planned number of cases was statistically set to 200 PDD-TURBT cases and 300 historical data cases, and the registration period was 2 years from January 2019 to December 2020, and the follow-up period was 2 years after second TUR. Results: In this study, 188 patients in the PDD-TURBT group and 313 patients in the historical group were enrolled, and 177 patients and 306 patients were included in the final analysis, respectively. After PSM adjustment, 167 patients in both groups were compared, and no significant differences were observed in age, gender, history of bladder cancer, tumor diameter, number of tumors, history of upper tract urothelial cancer, and period from initial TURBT to second TUR. The tumor residual rate was 25.8% in the PDD-TURBT group compared with 47.3% in the historical group, showing a significant decrease (odds ratio 0.39 [95% CI: 0.24–0.63]; p = 0.000064). Logistic regression analysis revealed that significant factors predicting residual tumors in PDD-TURBT were current or past smoking history, multiple tumors, and non-pTa (pT1 or pTis) tumors. Focusing on these three factors, patients with 0–1 of these three factors have a significant less tumor residual rate compared with patients with 2–3 factors (8.33% vs. 33.3%; odds ratio 5.46 [95% CI: 1.81–22.3]; p = 0.00052). Conclusions: PDD-TURBT for high-risk NMIBC significantly reduced the tumor residual rate at the second TUR compared to the conventional TURBT. PDD-TURBT using 5-ALA may enable to omit second TUR in some high-risk NMIBC cases. Clinical trial information: UMIN000035712.
Response: Re: Systematic Pelvic Lymphadenectomy vs No Lymphadenectomy in Early-Stage Endometrial Carcinoma: Randomized Clinical Trial
Authors: P. B. Panici, S. Basile, C. De Falco, A. A. Lissoni, M. Signorelli, D. Giannarelli, R. Fossati
Journal: JNCI Journal of the National Cancer Institute (2009)
Instructive Hydrogels for Primary Tumor Cell Culture: Current Status and Outlook
Authors: Yiyang Jia, Zhentong Wei, Songling Zhang, Bai Yang, Yunfeng Li
Journal: Advanced Healthcare Materials (2022)

Primary tumor organoids (PTOs) growth in hydrogels have emerged as an important in vitro model that recapitulates many characteristics of the native tumor tissue, and have important applications in fundamental cancer research and for the development of useful therapeutic treatment. This paper begins with reviewing the methods of isolation of primary tumor cells. Then, recent advances on the instructive hydrogels as biomimetic extracellular matrix for primary tumor cell culture and construction of PTO models are summarized. Emerging microtechnology for growth of PTOs in microscale hydrogels and the applications of PTOs are highlighted. This paper concludes with an outlook on the future directions in the investigation of instructive hydrogels for PTO growth.
Special Studies
Journal: JAMA (1966)

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
Neonatal morbidity and nursery function
Authors: M. M. Desmond
Journal: JAMA (1970)

In 6,211 live-born infants born to mothers of low socioeconomic status, approximately one half received routine care, one quarter were held for evaluation, and one quarter manifested morbidity (illness or malformation). In term infants morbidity was low, but the number of sick infants was high; the reverse was true of low-birth-weight infants. Morbidity-to-death ratios were 37:1 in term infants, and 5:1 in low-birth-weight infants. Ten percent of survivors had a known problem at discharge. To permit the rapid application of present knowledge, changes in philosophy of nursery care are necessary. Traditional nurseries operate on the assumption that newborn infants are healthy until proved ill. A nursery functioning on the assumption that all newly born infants are potentially ill until good health is demonstrated may offer advantages.
Metabolism, New York
Journal: JAMA (1964)

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
Human epidermal growth factor receptor 2 (HER2) and fibroblast growth factor receptor 3 (FGFR3) mutations to reveal biological pathways in urothelial carcinoma.
Authors: Carissa Ellen Chu, Manuel De Jesus Escano, Wesley Yip, Song Jiang, Gopa Iyer, Hikmat A. Al-Ahmadie, Alvin C. Goh, Guido Dalbagni, Bernard H. Bochner, David B. Solit, Eugene J. Pietzak
Journal: Journal of Clinical Oncology (2022)

567 Background: Human epidermal growth factor receptor 2 (HER2) (gene name: ERBB2) is a member of the epidermal growth factor receptor (EGFR) family and when mutated, associated with higher grade and stage of localized bladder cancer. Two HER2-targeted antibody-drug conjugates (ADC), trastuzumab emtansine and trastuzumab deruxtecan, are currently approved by the Food and Drug Administration (FDA) for use in gastric/breast cancers with promising application in urothelial carcinoma. Fibroblast growth factor receptor 3 ( FGFR3) is the target of another FDA-approved tyrosine kinase inhibitor erdafitinib and generally associated with more favorable prognosis as well as upper tract carcinoma. The purpose of this study is to characterize ERBB2 and FGFR3 mutations in a prospectively collected cohort of urothelial cancers. Methods: Patients with localized upper or lower tract urothelial carcinoma diagnosed between 2014 and 2020 who underwent a targeted exome sequencing panel of up to 468 cancer genes were identified. If multiple tumors were sequenced, only the diagnostic specimen was included. Analysis of gene alterations, frequency, and associated co-mutations was performed. Descriptive statistics were used to compare baseline patient characteristics. Results: 381 unique ERBB2 or FGFR3 mutated urothelial carcinoma specimens were included in this study. Of note, ERBB2 and FGFR3 mutations were essentially mutually exclusive and included 122 (66%) ERBB2 mutated tumors and 259 (34%) FGFR3 mutated tumors. Patients with tumors harboring FGFR3 mutations were younger (median 70 years IQR 60-76 vs. 74 years IQR 66-78, p&lt;0.05), while patients with ERBB2 mutated tumors were more likely to be male (85% vs 73%, p&lt;0.05). At the time of diagnosis, ERBB2 tumors were more likely to present with advanced (pT2 or higher) disease compared to FGFR3 mutated tumors (48% vs 24%). ERBB2 mutated tumors were more likely associated with RB1, P53, and ARID1A mutations, while FGFR3 mutated tumors were more likely associated with CDKN2A/B and STAG2 mutations (Table). Conclusions: These data highlight divergent biological pathways for patients with targetable mutations in ERBB2 and FGFR3 and are consistent with prior findings in non-muscle invasive bladder cancer. ERBB2 mutated tumors are associated with male gender, more aggressive pathological features and co-mutations with RB1, P53, and ARID1A.[Table: see text]
Self-castration
Authors: R. D. N. Bisset
Journal: BMJ (1949)

MEDICAL MEMORANDA BRJous 5He had been quite well until the evening of Dec. 9, when he suddenly felt tired, shivery, and generally " out of sorts," and complained of sore throat and pains in both shoulders and upper arms.Next day these symptoms were still present, with frontal headache and dizziness on moving about.On Dec. 11 he started to get pains and stiffness in the knees, ankles, wrists, and elbows.He noticed that his left knee was swollen.He vomited twice that day.On admission to hospital he felt weak and ill, his throat was still sore, and the joint pains were still severe.He had also constant dull pain in the precordial area.His appetite, normally good, had been poor since the onset of symptoms and he had become constipated.There was no cough or sputum; nor were there any urinary symptoms.On examination he was flushed and ill, the tongue was moist and coated, and the throat slightly injected.The mucosae were normal.No rash, no palpable nodes, and no cyanosis or clubbing were present.The temperatture was 1000 F. (37.8°C.), pulse 94, and respirations 20.The heart was not clinically enlarged.The heart sounds were normal at all areas; there were no murmurs.The blood pressure was 130/75.Respiratory system : no dullness ; sounds vesicular all areas no adventitious sounds.The abdomen was lax, with some tenderness in the left upper quadrant.The liver, spleen, and kidneys were not palpable.The central nervous system showed no disease.There was pain on passive movement of wrists, elbows, knees, and ankles, with redness and swelling of the left knee.The urine showed no abnormality.On x-ray examination the heart and lungs appeared normal.White blood cells
Malignant hyperpyrexia.
Authors: M A Denborough, F J Hird, J O King
Journal: BMJ (1971)

Superannuation in an Inte.atedHealth Service SER,-A Scottish joint working party concluded' that the case for integration of medical work is overwhelming and that a breaking down of artificial barriers between general practice, specialist practice, and com- munity medicine is overdue.I suggest that, especially in times of inflation, different superannuation regulations may hamper integration by complicating and, in some cases, penalizing, transfer from hospital or community medicine to general practice, or vice versa.
Pessary Plus Progesterone Tested in Pregnancies With Short Cervix
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fatal Cardiac Tamponade
Authors: Robert E. Sheep
Journal: JAMA (1982)

A case of fatal cardiac tamponade caused by superior vena cava perforation complicating left internal jugular vein catheterization and infusion is reported. Two cases of nonfatal combined hydromediastinum and hydrothorax as a result of the left-sided approach are discussed. Unexplained hypotension with venous distention in a patient with a central venous catheter should immediately raise the possibility of cardiac tamponade. Avoidance of the left internal jugular vein approach, the use of flexible catheter materials, and localization of the catheter tip above the pericardial reflection will lessen the complications caused by placement of central venous lines. (<i>JAMA</i>1982;248:1632-1635)
EXPERIMENTAL HYDROCEPHALUS
Authors: Walter S. Thomas
Journal: The Journal of Experimental Medicine (1914)

Internal hydrocephalus can be produced experimentally by injecting a foreign substance into the ventricles. In these experiments, aleuronat, a granular, insoluble material, has caused an acute inflammatory reaction, characterized in the first week by an exudate consisting largely of polynuclear leucocytes. Later the picture is one of a chronic process; polynuclear cells are replaced by lymphoid and large mononuclear cells and there is proliferation of the connective tissue in the choroid plexus. Proliferation of the ependyma occurs in the first week but becomes more advanced in the second and third weeks, and there is increase in neuroglia more marked in the long continued experiments. Ordinarily when aleuronat is injected into a serous cavity, the pleural cavity, for example, abundant accumulation of fluid takes place in twenty-four to forty-eight hours, and at the same time polynuclear leucocytes collect. In the experiments in which the irritant was injected into the ventricle of the brain there was little or no dilatation apparent in the first week; absence of dilatation in all probability is due to the free outflow of the fluid. When obstruction occurs during the chronic stage of the inflammatory process dilatation of the ventricle follows. Choked disc and other symptoms of increased intracranial pressure accompany experimental hydrocephalus. Dilatation occurs slowly and reaches a maximum in about two months. In some of the experiments of longer duration obstruction can be demonstrated in gross or microscopically. Obvious obstruction has not been found by gross examination in all instances, but in the experiments in which India ink was injected into the ventricle before death obstruction to outflow was very readily demonstrated. The third and fourth ventricles were in all instances filled with the pigment, but none appeared on the surface of the brain, whereas in normal dogs the entire surface, especially the base, became deeply pigmented. Obstruction to the circulation of cerebrospinal fluid causing internal hydrocephalus may occur at the foramen of Monro, in the aqueduct of Sylvius, or, doubtless with greatest frequency, at the foramen of Magendie.