tbuckley/cabot-search huggingface dataset:
Novel malignant-mesothelioma-associated antigens (Gene-X and THBS-2) in the diagnosis of malignant pleural mesothelioma (MPM).
Authors: Fumihiro Tanaka, Yoshiki Shigematsu, Takeshi Hanagiri, Hidetaka Uramoto, Tomoko So, Kazue Yoneda, Teruhisa Takuwa, Masaki Hashimoto, Seiji Matsumoto, Yoshitomo Okumura, Nobuyuki Kondo, Seiki Hasegawa
Journal: Journal of Clinical Oncology (2012)

10585 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor of the pleura associated with asbestos exposure, and its diagnosis is usually difficult at early stage. We identified novel mesothelioma-related antigens, Gene-X and thrombospondin-2 (THBS-2), recognized by tumor-infiltrating B cells (Cancer Sci 2009), but the clinical significance in the diagnosis of MPM remains unclear. Methods: A total of 120 patients, who presented with a suspicion of MPM and received pleural biopsy, were reviewed; 97 patients were finally diagnosed with MPM and 27 were with non-malignant diseases (NM). The antibody-titers against Gene-X and THBS-2 in the sera were measured by ELISA method. Results: The serum antibody-titer against THBS-2 was significantly higher in MPM patients than in NM (P&lt;0.01), but there was no difference in the serum antibody-titer against Gene-X (Table). The receiver operating characteristic (ROC) curve analysis showed a significant diagnostic value of serum antibody-titer against THBS-2 with the area-under curve of 0.886 (95% CI, 0.797 - 0.975; P&lt;0.001) in discrimination of MPM from NM diseases; the sensitivity and specificity, when the cut-off value was 0.08, were 72.2% and 95.5%, respectively. Conclusions: The serum antibody-titer against THBS-2 can be a useful non-invasive marker in the diagnosis of MPM. [Table: see text]
PET imaging urothelial bladder cancer: A novel approach.
Authors: Mathew L. Thakur, Leonard G. Gomella, Sushil K. Tripathi, Ebru Salmanoglu, Scott W. Keith, William Kevin Kelly, Jean H. Hoffman-Censits, Sung Kim, Charles M. Intenzo, Peter McCue, Edouard John Trabulsi
Journal: Journal of Clinical Oncology (2020)

443 Background: Urothelial bladder cancer (UBC) inflicts &gt;80,000 new patients annually. Since treatment is stage-dependent, accurate staging is crucial. Conventional imaging and biopsy are often unreliable. A large number of PET tracers, developed to improve imaging, have limitations e.g. urinary excretion compromising their ability to assess the bladder lumen and invasive tumors. This study is to validate a hypothesis that high density VPAC receptors expression on UBC cell surface, can be targeted to PET image UBC, to determine loco-regional disease and metastatic lesions. Methods: Cu-64-TP3805 (4±10% mCi), with its high affinity (3.1 x 10 −9M ) for VPAC, was given IV to 19 UBC patients (44-80 yrs), scheduled for radical cystectomy. Those eligible for neoadjuvant chemotherapy were treated as such. Urine and blood samples were collected on the day of scan. Whole body PET/CT images acquired 60 to 90 min later and read by two physicians. Surgery was performed 1 to 4 weeks later. Imaging results were correlated with histology. Results: There were no adverse events. Urinary excretion of Cu-64-TP3805 was negligible. Blood clearance was biphasic (t ½ a = 22.3 ±2.7 min ~ 85% and t ½ β = 118.2 ± 4.9 min ~ 15%). VPAC PET bladder images were true positive (TP) in 11, true negative (TN) in 4, false positive (FP) in 1 and false negative (FN) in 3 patients with 79% sensitivity (95% CI 49%-95%), 80% specificity (95% CI 28%-100%), 92% PPV (95% CI 62%-100%), and 57% NPV (95% CI 18%-90%). Prostate images were TP in 8, TN in 6, and FP in 5 patients, with 100% sensitivity (95% CI 63%-100%), 55% specificity (95% CI 23%-83%), 62% PPV (95% CI 32%-86%), and 100% NPV (95% CI 54%-100%). The 5 FP images revealed HGPIN on re-analysis. For lymph nodes, images were TP in 1, TN in 14 and FN in 4 patients, with 25% sensitivity (95% CI 1%-81%), 100% specificity (95% CI 78%-100%), 100% PPV (95% CI 3%-100%), and 83% NPV (95% CI 59%-96%). In one patient, several lesions were seen in the spine and iliac crest. Biopsy was positive for metastasis. In smokers (N=12) there was diffused or focal tracer uptake in the lungs. In 7 non-smokers, 3 with CT depicted abnormality had tracer lung uptake and 4 did not. Conclusions: These first in human pilot study data depict Cu-64-TP3805 VPAC targeting to image UBC as worthy of further investigation.
Association between the proportion of Plasmodium falciparum and Plasmodium vivax infections detected by passive surveillance and the magnitude of the asymptomatic reservoir in the community: a pooled analysis of paired health facility and community data
Authors: Gillian Stresman, Nuno Sepúlveda, Kimberly Fornace, Lynn Grignard, Julia Mwesigwa, Jane Achan, John Miller, Daniel J Bridges, Thomas P Eisele, Jacklin Mosha, Pauline Joy Lorenzo, Maria Lourdes Macalinao, Fe Esperanza Espino, Fitsum Tadesse, Jennifer C Stevenson, Antonio M Quispe, André Siqueira, Marcus Lacerda, Shunmay Yeung, Siv Sovannaroth, Emilie Pothin, Joanna Gallay, Karen E Hamre, Alyssa Young, Jean Frantz Lemoine, Michelle A Chang, Koukeo Phommasone, Mayfong Mayxay, Jordi Landier, Daniel M Parker, Lorenz Von Seidlein, Francois Nosten, Gilles Delmas, Arjen Dondorp, Ewan Cameron, Katherine Battle, Teun Bousema, Peter Gething, Umberto D'Alessandro, Chris Drakeley
Journal: The Lancet Infectious Diseases (2020)

Passively collected malaria case data are the foundation for public health decision making. However, because of population-level immunity, infections might not always be sufficiently symptomatic to prompt individuals to seek care. Understanding the proportion of all Plasmodium spp infections expected to be detected by the health system becomes particularly paramount in elimination settings. The aim of this study was to determine the association between the proportion of infections detected and transmission intensity for Plasmodium falciparum and Plasmodium vivax in several global endemic settings.
Whole Genome Sequencing Analyses Identify SIDT2 Loss-of-function Mutations In Patients with Eczema Herpeticum
Authors: Lianghua Bin, Claire Malley, Patricia Taylor, Meher Preethi Boorgula, Sameer Chavan, Malaika Mathias, Nicholas Rafaels, Ingo Ruczinski, Brittany Richers, Kathleen Barnes, Donald Leung, Rasika Mathias
Journal: Journal of Allergy and Clinical Immunology (2020)
Ce and Er Co-doped TiO2 for rapid bacteria- killing using visible light
Authors: Yawei Ren, Yajing Han, Zhaoyang Li, Xiangmei Liu, Shengli Zhu, Yanqin Liang, Kelvin Wai Kwok Yeung, Shuilin Wu
Journal: Bioactive Materials (2020)

Bacterial infection and related diseases are threatening the health of human beings. Photocatalytic disinfection as a simple and low-cost disinfection strategy is attracting more and more attention. In this work, TiO
Phase I study of AMG 160, a half-life extended bispecific T-cell engager (HLE BiTE) immune therapy targeting prostate-specific membrane antigen (PSMA), in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ben Tran, Lisa Horvath, Tanya B. Dorff, Richard Greil, Jean-Pascal H. Machiels, Felicia Roncolato, Karen A. Autio, Matthew Rettig, Karim Fizazi, Martijn P. Lolkema, Anthony C. Fermin, Mark Salvati, Hosein Kouros-Mehr
Journal: Journal of Clinical Oncology (2020)

TPS261 Background: AMG 160 is a novel HLE BiTE immune therapy that redirects T cells to kill tumor cells by binding to PSMA on tumor cells and CD3 on T cells. Methods: Primary objectives of this open-label, ascending, multiple-dose, phase 1 study (NCT03792841) are to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 160 in men with mCRPC; secondary objectives are to characterize pharmacokinetics (PK) and evaluate preliminary efficacy. The dose exploration will estimate the MTD or RP2D by Bayesian logistic regression modeling. The dose expansion will assess safety, efficacy, PK, and pharmacodynamics (PD) of the selected dose and provide further safety and efficacy data. PD biomarkers and potential patient selection biomarkers will be explored. Preliminary antitumor activity will be assessed by objective response per RECIST 1.1 with PCWG3 modifications, PSA response, duration of response, time to progression, PFS (radiographic and PSA)/OS, and circulating tumor cell (CTC) response (CTC0 and CTC conversion). Imaging will include CT/MRI, bone scan, 68 Ga-PSMA-11 PET/CT, and 18 F-FDG PET/CT. In cycle 1, patients will be pretreated with dexamethasone before short-term IV infusion of AMG 160 and will be hospitalized for 72 h after each AMG 160 dose. Key inclusion criteria: age ≥18 y; histologically/cytologically confirmed mCRPC that progressed after novel hormone therapy; failure of 1–2 taxane-based regimens or have refused a taxane regimen; bilateral orchiectomy or continuous androgen-deprivation therapy; evidence of progressive disease; total serum testosterone ≤50 ng/dL. Key exclusion criteria: active autoimmune disease or diseases requiring immunosuppressive therapy (low-dose prednisone permitted); CNS metastases, leptomeningeal disease, or spinal cord compression; prior PSMA-targeted therapy ( 177 Lu-PSMA-617 may be allowed). The study will enroll 30–50 patients in the dose exploration and 50 patients in the dose expansion globally. The study opened in January 2019; dose exploration is ongoing. Clinical trial information: NCT03792841.
Clinical utility of PSA density and PI-RADS for deferring biopsy for the detection of clinically significant prostate cancer.
Authors: Matthew Truong, Erica Stevens, Ryan Ward, Jennifer Bullen, Ethan Austhof, Rogelio Valdez, Andrei Purysko, Eric A. Klein
Journal: Journal of Clinical Oncology (2020)

298 Background: We sought to identify PSA density (PSAD) and Prostate Imaging-Reporting and Data Systems (PI-RADS) category cut-offs that would allow deferring biopsy in men with suspicion for clinically significant prostate cancer (csPCa). Methods: Our institution’s prostate MRI registry (n = 1718) was queried for patients who had MRI-guided biopsy (MRI-GB) and/or systematic biopsy (SB) performed after prostate MRI between January 2013 and October 2018 (n = 676). Patients in the diagnostic group (either biopsy naïve or with prior negative biopsy) and patients with PCa on active surveillance (AS) were considered eligible. PSA, PSAD, and PI-RADS category were entered into logistic regression models for predicting csPca (grade group [GG] ≥ 2) at biopsy. Receiver operating characteristic (ROC) analysis was performed to assess model accuracy and results were stratified by biopsy indication and PI-RADS categories. Results: Logistic regression models that combined PSAD and PI-RADS categories had the highest ROC’s in both the diagnostic and AS groups (AUC=0.830 and 0.778, respectively). For diagnostic group patients with PSAD ≤0.15, csPCa was found in 6/89 (6.7%) of negative MRI patients (i.e. PI-RADS ≤ 2), 4/90 (4.4%) of PI-RADS 3 patients, 59/159 (37%) of PI-RADS 4-5 patients. If a PSAD cutoff of ≤ 0.15 and PI-RADS category ≤ 3 MRI were used in combination as criteria for biopsy deferral, only 10/526 (1.9%) of patients would have had csPCa missed on subsequent biopsy. Among patients in the AS group with a negative MRI, 0/22(0%) and 3/8 (37.5%) had csPCA if the PSAD was ≤0.15 and &gt;0.15, respectively. Conclusions: For the diagnostic group of patients undergoing prostate biopsy, PSAD cut off ≤0.15 is useful for deferring biopsy only in patients with a PI-RADS ≤ 3. Confirmatory biopsy in patients should be strongly considered before enrolling patients in AS even in the setting of a negative MRI if the PSAD is &gt; 0.15.
Developing the ethical framework of end-stage kidney disease care: from practice to policy
Authors: Valerie A. Luyckx, Dominique E. Martin, Mohammed Rafique Moosa, Aminu K. Bello, Ezequiel Bellorin-Font, Tak Mao Chan, Rolando Claure-Del Granado, Walter Douthat, Somchai Eiam-Ong, Felicia U. Eke, Bak Leong Goh, Vivekanand Jha, Evie Kendal, Adrian Liew, Yewondwossen Tadesse Mengistu, Elmi Muller, Ikechi G. Okpechi, Eric Rondeau, Manisha Sahay, Michele Trask, Tushar Vachharajani
Journal: Kidney International Supplements (2020)
miR-17-5p and miR-20a-5p suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop
Authors: Dong-Li Liu, Li-Li Lu, Li-Li Dong, Yang Liu, Xin-Yu Bian, Bao-Feng Lian, Lu Xie, Duo Wen, Dong-Mei Gao, Ai-Wu Ke, Jia Fan, Wei-Zhong Wu
Journal: Theranostics (2020)

Dysregulation of microRNA (miRNA) is a frequent event in hepatocellular carcinoma (HCC), but little is known whether it is a bystander or an actual player on residual HCC metastasis during liver microenvironment remodeling initiated by hepatectomy.Methods: The differently expressed miRNAs and mRNAs were identified from RNA-seq data.Western blot, qRT-PCR, fluorescence in situ hybridization, immunofluorescence and immunohistochemical were used to detect the expression of miRNA and mRNA in cell lines and patient tissues.The biological functions were investigated in vitro and in vivo.Chromatin immunoprecipitation, proximity ligation and luciferase reporter assay were used to explore the specific binding of target genes.The expression of HGF/ERBB3 signaling was detected by Western blot.Results: In this study, HGF induced by hepatectomy was shown to promote metastasis of residual HCC cells.miR-17-5p and miR-20a-5p were confirmed to play inhibitory roles on HCC metastasis.And ERBB3 was found to be the common target of miR-17-5p and miR-20a-5p.HCC cells with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 were often more sensitive to response HGF stimuli and to facilitate metastatic colonization both in vitro and in vivo experimental systems.Furthermore, HGF reinforced ERBB3 expression by NF-κB transcriptional activity in a positive feedback loop.Of particular importance, HCC patients with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 had significantly shorter OS and PFS survivals after surgical resection.Conclusion: miR-17-5p and miR-20a-5p could suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop and offer a new probable strategy for metastasis prevention after HCC resection.
Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis
Authors: Myrthe M van Dijk, Astrid M Kolte, Jacqueline Limpens, Emma Kirk, Siobhan Quenby, Madelon van Wely, Mariëtte Goddijn
Journal: Human Reproduction Update (2019)

Abstract BACKGROUND Recurrent pregnancy loss (RPL) occurs in 1–3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79–1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86–1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55–1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06–4.56). WIDER IMPLICATIONS A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.
Screening for Lung Cancer — 10 States, 2017
Authors: Thomas B. Richards, Ashwini Soman, Cheryll C. Thomas, Brenna VanFrank, S. Jane Henley, M. Shayne Gallaway, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Lung cancer is the leading cause of cancer death in the United States; 148,869 lung cancer-associated deaths occurred in 2016 (1). Mortality might be reduced by identifying lung cancer at an early stage when treatment can be more effective (2). In 2013, the U.S. Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low-dose computed tomography (CT) for adults aged 55-80 years who have a 30 pack-year* smoking history and currently smoke or have quit within the past 15 years (2).† This was a Grade B recommendation, which required health insurance plans to cover lung cancer screening as a preventive service.§ To assess the prevalence of lung cancer screening by state, CDC used Behavioral Risk Factor Surveillance System (BRFSS) data¶ collected in 2017 by 10 states.** Overall, 12.7% adults aged 55-80 years met the USPSTF criteria for lung cancer screening. Among those meeting USPSTF criteria, 12.5% reported they had received a CT scan to check for lung cancer in the last 12 months. Efforts to educate health care providers and provide decision support tools might increase recommended lung cancer screening.
Response to systemic therapy in patients with metastatic fumarate hydratase (FH) deficient renal cell carcinoma (RCC).
Authors: Jack Patrick Gleeson, Ines Nikolovski, Ritesh Kotecha, Yasser Ged, Natalie Shapnik, Andrea Knezevic, Darren R. Feldman, Chung-Han Lee, Martin H Voss, Ying-Bei Chen, Robert J. Motzer, Maria Isabel Carlo
Journal: Journal of Clinical Oncology (2020)

686 Background: FH-deficient RCC (FHRCC) is characterized by unique pathologic features and lack of FH staining on immunohistochemistry (IHC). Most cases are associated with germline FH mutations and poor prognosis, but there is limited data on the efficacy of systemic therapy. Methods: Patients with metastatic FHRCC, defined by presence of FH germline or somatic mutation with loss of FH by IHC [FH and 2-succino-cysteine (2SC)], were identified from an institutional database. Clinical and treatment data was obtained from electronic records. The primary outcome was best objective response rate to first, second or third-line systemic therapy by blinded investigator RECIST v1.1 assessment. Results: 32 patients (median age 46; range 20-74; M:F, 20:12) were identified. All patients had evidence of FH-deficiency by IHC, 23 (72%) had germline FH mutations, 9 (28%) had somatic only FH mutations. 20 patients (62.5%) presented with de novo metastatic disease. Most common sites of metastasis were retroperitoneal lymph nodes (82%), lung (78%) and peritoneal spread (70%); no patients developed brain metastases. Median overall survival (OS) from diagnosis of metastatic disease is 28.1 months (95% CI: 14.9, 33.8). Median follow-up is 14.8 months. 25 patients were evaluable for response to first-line therapy, 5 to second-line and 4 to third-line therapy (Table). Most common first-line therapies were combination mTOR/VEGFR (50%) and VEGFR monotherapy (20%). ORR to first, second and third-line therapy was 40%, 20% and 25%, with no complete responses. 8 patients who received IO monotherapy were evaluable; 3 had stable disease, no responses were seen. Conclusions: Patients with FHRCC show distinct patterns of disease progression with primary peritoneal spread. Although there was high ORR to VEGFR/mTOR inhibitor combinations, there were limited responses to IO monotherapy.[Table: see text]
Adding mitomycin to Bacillus Calmette-Guérin as adjuvant intravesical therapy for high-risk, nonmuscle-invasive urothelial bladder cancer (BCGMM; ANZUP 1301).
Authors: Elizabeth Chien Hern Liow, Dickon Hayne, Martin R. Stockler, Andrew James Martin, Shomik Sengupta, Paul Anderson, Kate Ford, Mark Frydenberg, Margot Gorzeman, Will Green, Jeremy Grummet, Cynthia Hawks, Laurence Eliot Miles Krieger, Joseph Ischia, Steve McCombie, Manish Patel, Ian D. Davis
Journal: Journal of Clinical Oncology (2020)

TPS602 Background: Adjuvant intravesical bacillus Calmette-Guérin (BCG) decreases disease recurrence and progression in people with high-risk, non-muscle invasive urothelial bladder cancer (NMIBC), however recurrence occurs in 30% despite optimal therapy. Recent meta-analyses evaluating addition of intravesical mitomycin (MM) to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Good quality randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will be the largest study to date evaluating this approach in people with high-risk NMIBC. Methods: This open-label phase 3 trial aims to randomize 500 participants, stratified by stage, site of disease, and presence of carcinoma in-situ, to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG + MM weekly x9 then monthly x9). This study is powered to detect a 10% improvement in 2-year disease free survival (DFS) at 5% level of significance with 85% power. Stage 1 of this study, designed to recruit 130 patients to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, has completed enrolment and successfully established feasibility of this trial protocol. Stage 2, aiming for a further 370 patients, will inform on additional endpoints including differences in DFS, time to recurrence and progression, overall survival, and potential predictive biomarkers, is estimated to complete accrual in December 2020. Successful treatment completion, defined as 75% or more of planned treatment doses, has been achieved in 76% of patients treated in the experimental arm of Stage 1, compared to 60% in those allocated BCG alone. Clinical trial information: NCT02948543.
Neural Mechanisms of Itch
Authors: Mark Lay, Xinzhong Dong
Journal: Annual Review of Neuroscience (2020)

Itch is a unique sensation that helps organisms scratch away external threats; scratching itself induces an immune response that can contribute to more itchiness. Itch is induced chemically in the peripheral nervous system via a wide array of receptors. Given the superficial localization of itch neuron terminals, cells that dwell close to the skin contribute significantly to itch. Certain mechanical stimuli mediated by recently discovered circuits also contribute to the itch sensation. Ultimately, in the spinal cord, and likely in the brain, circuits that mediate touch, pain, and itch engage in cross modulation. Much of itch perception is still a mystery, but we present in this review the known ligands and receptors associated with itch. We also describe experiments and findings from investigations into the spinal and supraspinal circuitry responsible for the sensation of itch.