tbuckley/cabot-search huggingface dataset:
THE DIET OF THE PRECIBICULTURISTS
Authors: H. Campbell
Journal: BMJ (1905)

DIET OF THE PREOIBIOULTURIST&.[DEm.23 19.but .everythird week begin a' very thorough examination of one school, and pay several visits a. short intervals till it s deemed sufficiently cleansed.The teachers should then endeavour to maintain the results of the nurse's work for weeks or months.Managers do not realize the amount of work a nurse has to do, and in many instances have sent in requests for more frequent visits from the nurse, or for greater attention to their particular school, which at present it is quite impossible to afford."Ringworm -It is estimated that loss of attendance owing to ringworm is about one ninth; absence may be prolonged over many months and even years.Favue.-Favus, which may be regarJed as a disease nearly allied to ringworm, chiefly occurs in the East End.It hasbeen decided to open an elementary school for favus caees only, to accommodate 8o children, a separate roomforanurse being provided.Unclean Heads -The number of unclean heads Is con- tinually diminishing.The methods of dealing with these eases are cumbersome and slow, and though the results are excellent, powers for a more rapid method of dealing with objectionable cases are required.The powers should be
Genetic Analysis of the Induction of Tumors by Methylcholanthrene. IX. Induced and Spontaneous Adenocarcinomas of the Stomach in Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Leonell C. Strong
Journal: JNCI Journal of the National Cancer Institute (1945)

Genetic Analysis of the Induction of Tumors by Methylcholanthrene. IX. Induced and Spontaneous Adenocarcinomas of the Stomach in Mice Get access Leonell C. Strong Leonell C. Strong associate professor Department of Anatomy, Yale University, School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 5, April 1945, Pages 339–362, https://doi.org/10.1093/jnci/5.5.339 Published: 01 April 1945
Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank
Authors: Sean J. Jurgens, Seung Hoan Choi, Valerie N. Morrill, Mark Chaffin, James P. Pirruccello, Jennifer L. Halford, Lu-Chen Weng, Victor Nauffal, Carolina Roselli, Amelia W. Hall, Matthew T. Oetjens, Braxton Lagerman, David P. vanMaanen, Goncalo Abecasis, Xiaodong Bai, Suganthi Balasubramanian, Aris Baras, Christina Beechert, Boris Boutkov, Michael Cantor, Giovanni Coppola, Tanima De, Andrew Deubler, Aris Economides, Gisu Eom, Manuel A. R. Ferreira, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Lukas Habegger, Alicia Hawes, Marcus B. Jones, Katia Karalis, Shareef Khalid, Olga Krasheninina, Rouel Lanche, Michael Lattari, Dadong Li, Alexander Lopez, Luca A. Lotta, Kia Manoochehri, Adam J. Mansfield, Evan K. Maxwell, Jason Mighty, Lyndon J. Mitnaul, Mona Nafde, Jonas Nielsen, Sean O’Keeffe, Max Orelus, John D. Overton, Maria Sotiropoulos Padilla, Razvan Panea, Tommy Polanco, Manasi Pradhan, Ayesha Rasool, Jeffrey G. Reid, William Salerno, Thomas D. Schleicher, Alan Shuldiner, Katherine Siminovitch, Jeffrey C. Staples, Ricardo H. Ulloa, Niek Verweij, Louis Widom, Sarah E. Wolf, Krishna G. Aragam, Kathryn L. Lunetta, Christopher M. Haggerty, Steven A. Lubitz, Patrick T. Ellinor
Journal: Nature Genetics (2022)
A Course of Lectures on Clinical Medicine
Authors: W. R. Basham
Journal: BMJ (1847)

L ECTtTRE VI.Case of Drunkard's Delirium, with pneumonia and bronchitis: History of the case; character of the delirium; stethoscopic signs; condition of the sputa; treatment: death; post-mortem appearances.-Ten-dency of drunkards to collapse; urgency of inflam- matory symptoms, when supervening in such cases.Physical signs ofpneumonia and bronchitis.-Patholoyicalcondition of pneumonia; cause of the rust- coloured sputa; progress of the disease.-Effects of bronchitis, complicated with pneumonia; discretion required in the treatment of such cases.Gentlemen,-You have been present this day at the post-mortem examination of two cases of acute disease of the pulmonary organs, which, tbough they do not exhibit any uncommon features, are nevertheless of interest to those who are engaged in pathological
Functionalized Mn<sub>3</sub>O<sub>4</sub> Nanosheets with Photothermal, Photodynamic, and Oxidase‐Like Activities Triggered by Low‐Powered Near‐Infrared Light for Synergetic Combating Multidrug‐Resistant Bacterial Infections
Authors: Xinwen Zhang, Yuanhong Min, Qi Zhang, Shiyue Wu, Wensheng Fu, Jiangling Wu, Ming Li, Yi Wang, Pu Zhang
Journal: Advanced Healthcare Materials (2022)

Multidrug-resistant (MDR) pathogenic bacterial infections have become a major danger to public health. Synergetic therapy through multiple approaches is more powerful than the respective one alone, but has been rarely achieved in defeating MDR bacterial infections so far. Herein, indocyanine green-functionalized Mn3 O4 nanosheets are engineered as an efficient and safe antibacterial agent with photothermal, photodynamic, and oxidase-like activities, which display powerful ability in treating MDR bacterial infections. Therein, photothermal and photodynamic activities can be triggered by a single low-powered near-infrared laser (808 nm, 0.33 W cm-2 ), resulting in the generation of localized hyperthermia (photothermal conversion efficiency, 67.5%) and singlet oxygen. Meanwhile, oxidase-like activity of this material further leads to the generation of hydroxyl radical as well as superoxide radical. Sheet-like structure with rough surfaces make them tends to adhere on bacterial surface and thus damage membrane system as well as influence bacterial metabolism. As a result, Gram-positive and Gram-negative bacteria can both be eradicated. Animal experiments further indicate that the functionalized Mn3 O4 nanosheets can effectively treat methicillin-resistant Staphylococcus aureus-infected wounds through the triple synergetic therapy. Moreover, toxicity evaluation in vitro and in vivo has proved the superior biosafety of this material, which is promising to apply in clinical anti-infective therapy.
Expanding the use of targeted therapy for urothelial bladder cancer (UBC): Non-<i>FGFR3</i> receptor tyrosine kinase (RTK) gene rearrangements (ReAr) and fusions (fus).
Authors: Andrea Necchi, Dean C. Pavlick, Gennady Bratslavsky, Joseph M Jacob, Oleksandr Kravtsov, Philippe E. Spiess, Petros Grivas, Vamsi Parini, Brennan Decker, Douglas I. Lin, Natalie Danziger, Mia Alyce Levy, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2022)

550 Background: After the regulatory approval of erdafitinib targeting FGFR genomic alterations (GA), molecular profiling and targeted therapy indications may further expand in UBC. We queried a large database of advanced UBC to study the landscape of RTK ReAr and Fus to categorize additional targets beyond FGFR1-3 that have potential to further personalize treatment of this disease. Methods: We analyzed data from 8,233 UBC cases, which underwent hybrid capture-based comprehensive genomic profiling (CGP). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression in tumor cells was assessed by IHC (Dako 22C3). Results: A total of 1,210 (14.7%) UBC featured known and likely large-scale (LS) internal ReAr with 414 (5%) ReAr in RTK genes. The ReAr/fus were distributed among ABL1 (3), ALK (3), BRAF (29), CDK12 (44), CDK8 (1), EGFR (10 ), ERBB2 (3), FGFR1 (2), FGFR2 (16 ), FGFR3 (231), FLT3 (1), MAO2K4 (4), NTRK1 (7 ), NTRK2 (5), NTRK3 (7), RAF1 (31 ), RET (8) and ROS1 (9). LS ReAr were divided into LS ReAr-associated gene deletions (1%), truncations (1%), rearrangements (61%) and fusions (37%). FGFR3 fus accounted for 81% of RTK fus with BRAF and RAF1 both at 2%. The greatest frequencies of kinase ReAr were in CDK12 (29%), FGFR3 (16%), RAF1 (13%) and BRAF (12%). Additional noteworthy ‘targetable’ RTK ReAR and fus included NTRK1-3 (19 cases), ROS1 (9 cases), RET (8 cases) and ALK (1 case). 407 (98.4%) of the RTK ReAr/fus-positive UBC had only 1 RTK ReAr/fus GA and 7 (1.6%) had 2 ReAr ReAr/fus, 6 (85.7%) of which involved FGFR3. Compared with LS ReAR negative UBC, the LS ReAR UBC cases revealed similar gender and age characteristics, MSI status, similar frequencies of TMB ≥ 10 mut/Mb and PD-L1 expression in tumor cells ≥1% and ≥50%. Conclusions: At a 5% frequency, potentially ‘targetable’ RTK gene rearrangements and fusions are a rare but important opportunity to further personalize treatment selection of UBC, including RTK inhibitors, PARP inhibitors ( CDK12) and immunotherapy. This potential for clinical trials supports broader CGP, compared to targeted FGFR sequencing, in order to uncover additional opportunities for precision therapies that have the potential to improve patient outcomes.[Table: see text]
Time varying association between deprivation, ethnicity and SARS-CoV-2 infections in England: A population-based ecological study
Authors: Tullia Padellini, Radka Jersakova, Peter J. Diggle, Chris Holmes, Ruairidh E. King, Brieuc C.L. Lehmann, Ann-Marie Mallon, George Nicholson, Sylvia Richardson, Marta Blangiardo
Journal: The Lancet Regional Health - Europe (2022)

Ethnically diverse and socio-economically deprived communities have been differentially affected by the COVID-19 pandemic in the UK.
Development and clinical application of PredicineBEACON next-generation minimal residual disease assay for genitourinary cancers.
Authors: Feng Xie, Jingyu Zang, Yue Zhang, Ruiyun Zhang, Yong Huang, Guanglei Zhuang, Haige Chen, Pan Du, Shidong Jia
Journal: Journal of Clinical Oncology (2022)

539 Background: Tumor-informed minimal residual disease (MRD) assay has been studied in muscle invasive bladder cancer (MIBC) in IMvigor010 study. However, the current methods require the use of tumor tissue and lacking actionable insights. In this study, a tumor-agnostic and actionable MRD assay (PredicineBEACON) is developed with high sensitivity and capability to detect actionable mutations in blood- or urine-based circulating tumor DNA. Methods: PredicineBEACON tumor-agnostic MRD assay includes three components, i.e., baseline mutation identification, personalized panel design, and ultra-deep next generation sequencing of cancer variants. Step 1: whole exon sequencing with boosted depth in 600 cancer-related genes is performed using baseline tumor tissue or liquid biopsy (blood or urine) to identify somatic mutations. Step 2: Up to fifty somatic mutations are selected for personalized MRD panel design, in combination with the use of a fixed core panel of 500 actionable/hotspot variants. Step 3: MRD and actionable mutations were called from ultra-deep sequencing (100,000X). A companion low-pass whole-genome sequencing (LP-WGS) is performed to monitoring copy number variation (CNV). In the current study of patients with MIBC, urine samples at baseline were used for personalized variant generation. Urine samples under neoadjuvant immunotherapy and blood samples after radical cystectomy were collected and tested with the PredicineBEACON MRD assay. Results: PredicineBEACON MRD assay demonstrated a sensitivity of 0.005% tumor fraction. In patients of MIBC, urine-based MRD assay detected the dynamic changing of disease evolution under neoadjuvant therapy and preceded the radiographic response. Actionable mutations, including FGFR3, TERT and PIK3CA mutations, were detected. Copy number burden revealed by LP-WGS correlated with disease evolution. Plasma-based MRD assay on the patients after radical cystectomy is currently ongoing. Conclusions: PredicineBEACON tumor-agnostic MRD assay provides an ultra-sensitive and actionable MRD detection with high sensitivity and specificity. Assessment of MRD could potentially be leveraged, for example, to avoid overtreatment of early stage of genitourinary cancers such as non-metastatic prostate cancer, non-muscle invasive bladder cancer and muscle invasive bladder cancer.
Prevalence of Stroke—United States, 2005
Journal: JAMA (2007)

Stroke is the third most common cause of death in the United States. Stroke also results in substantial health-care expenditures; the mean lifetime cost resulting from an ischemic stroke is estimated at $140,000 per patient. Nationwide, costs related to stroke are expected to reach an estimated $62.7 billion in 2007. Stroke death rates are higher in the southeastern United States, compared with other regions of the country; blacks, American Indians/Alaska Natives (AI/ANs), Asians/Pacific Islanders, and Hispanics die from stroke at younger ages than whites. Regional and national data on self-reported stroke prevalence have been published previously; however, state-specific prevalence data for persons with a history of stroke have not. To provide national-level stroke prevalence estimates by age group, sex, race/ethnicity, and education level and overall prevalence estimates for each of the 50 states, the U.S. Virgin Islands (USVI), the District of Columbia (DC), and Puerto Rico, CDC analyzed data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report summarizes the results of that analysis and provides the first state-based prevalence estimates of stroke. The results indicated that, in 2005, substantial differences existed in the prevalence of stroke by state/territory, race/ethnicity, age group, and education level. To lower the incidence of stroke and meet the Healthy People 2010 objective to reduce stroke deaths (objective no. 12-7) and the overall goal to eliminate health disparities, public health programs should augment stroke risk-factor prevention and educational measures in disproportionately affected regions and populations.
Phase Ib study of avelumab and taxane based chemotherapy in platinum-refractory or ineligible metastatic urothelial cancer (AVETAX study).
Authors: Rohan Garje, Vignesh T. Packiam, Amy Koski, Mohammed M. Milhem, Michael A. O'Donnell, Yousef Zakharia
Journal: Journal of Clinical Oncology (2022)

503 Background: Metastatic urothelial cancer is aggressive and associated with dismal 5-yr overall survival. Platinum-based chemotherapy and checkpoint inhibitors are standard first-line options with enfortumab vedotin, sacituzumab govitecan, and erdafitinib (in select FGFR altered tumors) subsequently utilized upon disease progression. However, despite these options, long-term outcomes remain poor, and novel strategies are needed to improve oncologic outcomes. We hypothesized that combining avelumab (anti-PD-L1 immunotherapy) with docetaxel is safe and will enhance cancer cell death by releasing neoantigens and potentiating anti-tumor immune-mediated cytotoxicity. Methods: This is a phase 1b, single-arm, open-label prospective clinical trial evaluating the combination of avelumab with docetaxel in adult subjects with locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. There are two phases. In Phase 1b, dose de-escalation of docetaxel (Level 0: 75, Level -1: 60 or Level -2: 45 mg/m2) with standard dose avelumab (10 mg/kg) aimed to establish the phase 2 dose in a standard 3+3 design. In dose-expansion, avelumab with the RP2D of docetaxel was evaluated for efficacy. The combination therapy is administered every 3 weeks for 6 cycles, and then avelumab alone is continued every 2 weeks. The primary endpoint is safety. Efficacy endpoints include objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: At the cutoff date of 10/8/2021, 21 patients were enrolled in the study. Only one of the 6 patients treated with level 0 dose of docetaxel had dose-limiting toxicity (neutropenic fever). Docetaxel at 75 mg/m2 along the avelumab was deemed safe for dose expansion cohort. An additional 15 patients were enrolled in the dose-expansion cohort. Of the 20 evaluable patients, ORR (CR+PR) was seen in 70% of subjects. (CR: 30%, PR: 40%, SD: 5%, PD: 25%, and 1 patient was not evaluable). The median PFS was 9.2 months (range: 1.5 – 25.8 months), and median OS was not reached. The most common Grade 3 or 4 AEs were febrile neutropenia, transaminitis, diarrhea, anemia, and neutropenia. No treatment-related deaths were noted. Conclusions: The combination of avelumab with docetaxel is safe with promising efficacy that is worth further studying in patients with platinum-refractory or ineligible metastatic urothelial cancer. Clinical trial information: NCT03575013.
Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.
Authors: Michael J. Morris, A. Oliver Sartor, Jeffrey Y.C. Wong, Steven I Max, Hong Xie, Mike Russell, Chaitanya R Divgi, Daniel Patricia, Anjali Narayan Avadhani, Luke T. Nordquist
Journal: Journal of Clinical Oncology (2022)

TPS206 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225 Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [ 111 In]-DOTA-h11B6, patients (pts) with mCRPC (progressed on standard therapies), treatment with a single dose of [ 111 In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in PK between 2 and 10 mg antibody mass (Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, pharmacokinetics (PK), pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of Sep 2021, 4 sites have been initiated and 14 pts enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.
Commentaire de travail de Jirapinyo P et al., pp. 532
Authors: Antoine Charachon
Journal: Endoscopy (2013)

See also: Evaluation of an endoscopic suturing device for transoral outlet reduction in patients with weight regain following Roux-en-Y gastric bypassEndoscopy 2013; 45(07): 532-536DOI: 10.1055/s-0032-1326638
Recombinant humanized Anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma (POLARIS-03 study): Two-year survival update and biomarker analysis.
Authors: Xinan Sheng, Haige Chen, Bin Hu, Xudong Yao, Ziling Liu, Xin Yao, Hongqian Guo, Yi Hu, Zhigang Ji, Hong Luo, Benkang Shi, Jiyan Liu, Jin WU, Fangjian Zhou, Zhisong He, Jinhai Fan, Yiran Huang, Jun Guo
Journal: Journal of Clinical Oncology (2022)

508 Background: Patients with advanced metastatic urothelial carcinoma (mUC) who experience disease progression after standard therapy have limited treatment options. Toripalimab was approved for the 2 nd line treatment of mUC based on a phase II clinical study (POLARIS-03) in Chinese patients with mUC (Clinical trial ID: NCT03113266). Here we report the two-year OS update and biomarker analysis of the study. Methods: Metastatic UC Patients received toripalimab 3 mg/kg Q2W until disease progression, unacceptable toxicity or voluntary withdrawal. Clinical response was assessed every 8 weeks. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated for correlation with clinical response. Results: From May 2017 to September 2019, 204 patients were screened and 151 patients were enrolled from 15 participating centers. By cutoff date of September 8, 2021, no emergent of new safety signal was identified compared with the previous one-year report. By the cutoff date, 91 patients have died, and the median OS was 14.6 months. Whole exome sequencing (WES) was performed on tumor biopsies and paired PBMCs and the results were available from 135 patients. Patients with mutations in chromatin remodelers SMARCA4/PBRM1 or tumor suppressor RB1 were associated with better responses to toripalimab than patients with wild-type genes. The ORR was 30% (6/20) in patients with FGFR2/FGFR3 mutations or FGFR2/FGFR3 gene fusions, and 42% (5/12) in patients with NECTIN4 genomic alternations. The median TMB value was 4.1 mutations per million base pairs (Mb) in the cohort. Using 10 mutations/Mb as the cut off, TMB-high patients (n = 27) had better ORR than TMB low patients(n = 108) (48% versus 22%, p = 0.014). The TMB-high group also showed better PFS (12.9 versus 1.8 months, HR = 0.48 [95% CI:0.31-0.74], p &lt; 0.001) and OS (not reached versus 10.0 months, HR = 0.53 [95% CI:0.32-0.88], p = 0.013) than the TMB low group. Conclusions: Toripalimab has demonstrated a manageable safety profile and encouraging clinical activity in metastatic UC patients refractory to 1 st line chemotherapy. WES analysis identified divergent mutations in the study. We report the utility of TMB to predict not only the response rate but also the PFS and OS benefits in patients with mUC in response to an ICI monotherapy. Clinical trial information: NCT03113266.