tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients
Authors: Madhav Prasad Yadav, Sanjana Ballal, Chandrashekhar Bal, Ranjit Kumar Sahoo, Nishikant Avinash Damle, Madhavi Tripathi, Amlesh Seth
Journal: Clinical Nuclear Medicine (2019)

Purpose The aim of this study was to evaluate the efficacy and safety of 177 Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). Methods In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68 Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent 177 Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients. Results The median age of patients was 66.5 years (range, 30–88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects. Conclusions 177 Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.
Ebv-Mir-BART11-3p, Ebv-Mir-BART9 and Ebv-Mir-BART10 Are Present in the Plasma of HIV-Infected Subjects with Lymphoma and Are Potential Lymphoma Biomarkers
Authors: Josep Muncunill, Maria Joao Baptista, Agueda Hernandez-Rodriguez, Judith Dalmau, Gustavo Tapia, Olga Garcia, Miriam Moreno, Juan-Manuel Sancho, Javier Martinez-Picado, Josep-Maria Ribera, Evarist Feliu, Jose-Luis Mate, Jose Tomas Navarro
Journal: Blood (2017)
A retrospective analysis of immune checkpoint therapy in patients with non-small cell lung cancer: Focus on thyroid disorder
Authors: S. Ono, H. Senju, H. Taniguchi, H. Tomono, M. Shimada, F. Hayashi, T. Suyama, N. Honda, Y. Umeyama, Y. Dotsu, H. Gyotoku, S. Takemoto, H. Yamaguchi, M. Fukuda, H. Soda, H. Mukae
Journal: Annals of Oncology (2019)
Proteomic Profiling of HTLV-1 Carriers and ATL Patients Reveal TNFR2 As a Novel Diagnostic and Chemosensitivity Biomarker for ATL
Authors: Carmina Louise Hugo Guerrero, Yoshiko Yamashita, Megumi Kuba-Miyara, Naoki Imaizumi, Shugo Sakihama, Masaki Hayashi, Takashi Miyagi, Satoko Morishima, Kennosuke Karube, Yuetsu Tanaka, Hiroaki Masuzaki, Takuya Fukushima
Journal: Blood (2019)
Colonic strictures mimicking Crohn’s disease
Authors: Kento Takenaka, Maiko Kimura, Kazuo Ohtsuka
Journal: Gut (2019)

A 38-year-old woman presented with a 3-month history of abdominal pain, diarrhoea and 2 kg weight loss. Plain CT performed initially revealed minor ascites, without any evidence of bowel inflammation or tumours. Considering the patient’s symptoms and age, IBD was suspected and colonoscopy was performed, which revealed nodular irregularity and a severe stricture in the sigmoid colon that prevented the passage of the scope. Colonic biopsy of the stricture revealed a normal epithelium. Because of the failure to obtain a definitive diagnosis, the patient was referred to our university hospital.

Laboratory tests revealed no anaemia …
Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients
Authors: Lenka Kasikova, Michal Hensler, Iva Truxova, Petr Skapa, Jan Laco, Lucie Belicova, Ivan Praznovec, Sarka Vosahlikova, Michael J. Halaska, Tomas Brtnicky, Lukas Rob, Jiri Presl, Jan Kostun, Isabelle Cremer, Ales Ryska, Guido Kroemer, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals<i>,</i> i.e., the exposure of calreticulin (CALR) on the membrane of malignant cells experiencing endoplasmic reticulum (ER) stress, is well known for its role in the activation of immune responses to dying cancer cells. However, the potential impact of CALR on the immune contexture of primary and metastatic high-grade serous carcinomas (HGSCs) and its prognostic value for patients with HGSC remains unclear. <h3>Method</h3> We harnessed a retrospective cohort of primary (no = 152) and metastatic (no = 74) tumor samples from HGSC patients to investigate the CALR expression in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 302 HGSC samples was used as a confirmatory approach. <h3>Results</h3> We demonstrate that CALR exposure on the surface of primary and metastatic HGSC cells is driven by a chemotherapy-independent ER stress response and culminates with the establishment of a local immune contexture characterized by T<sub>H</sub>1 polarization and cytotoxic activity that enables superior clinical benefits. <h3>Conclusions</h3> Our data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.
USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation
Authors: Sunbin Ling, Qiaonan Shan, Qifan Zhan, Qianwei Ye, Peng Liu, Shengjun Xu, Xin He, Jian Ma, Jiajia Xiang, Guangjiang Jiang, Xue Wen, Zijie Feng, Yuan Wu, Tingting Feng, Li Xu, Kangchen Chen, Xuanyu Zhang, Rongli Wei, Chenzhi Zhang, Beini Cen, Haiyang Xie, Penghong Song, Jimin Liu, Shusen Zheng, Xiao Xu
Journal: Gut (2019)

Objective We aimed to elucidate the mutual regulation mechanism of ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor-1α (HIF1α), and the mechanism they promote the stemness of hepatocellular carcinoma (HCC) cells under hypoxic conditions. Design Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were established to detect the stemness of HCC cells. Immunoprecipitation, ubiquitination assay and chromatin immunoprecipitation assay were used to elucidate the mutual regulation mechanism of USP22 and HIF1α. HCC patient samples and The Cancer Genome Atlas data were used to demonstrate the clinical significance. In vivo USP22-targeting experiment was performed in mice bearing HCC. Results USP22 promotes hypoxia-induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1α. As direct target genes of HIF1α, USP22 and TP53 can be transcriptionally upregulated by HIF1α under hypoxic conditions. In TP53 wild-type HCC cells, HIF1α induced TP53-mediated inhibition of HIF1α-induced USP22 upregulation. In TP53-mutant HCC cells, USP22 and HIF1α formed a positive feedback loop and promote the stemness of HCC. HCC patients with a loss-of-function mutation at TP53 and high USP22 and/or HIF1α expression tend to have a worse prognosis. The USP22-targeting lipopolyplexes caused high tumour inhibition and high sorafenib sensitivity in mice bearing HCC. Conclusion USP22 promotes hypoxia-induced HCC stemness by a HIF1α/USP22 positive feedback loop on TP53 inactivation. USP22 is a promising target for the HCC therapy.
Diagnosis of Pulmonary Embolism with <scp>d</scp>-Dimer Adjusted to Clinical Probability
Authors: Clive Kearon, Kerstin de Wit, Sameer Parpia, Sam Schulman, Marc Afilalo, Andrew Hirsch, Frederick A. Spencer, Sangita Sharma, Frédérick D’Aragon, Jean-François Deshaies, Gregoire Le Gal, Alejandro Lazo-Langner, Cynthia Wu, Lisa Rudd-Scott, Shannon M. Bates, Jim A. Julian
Journal: New England Journal of Medicine (2019)

Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP. We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism. A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9). A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).
Intimate partner violence is just one element of “intimate terrorism”
Authors: Jeremy Gibson, Zabaida Anwar
Journal: BMJ (2019)

We are concerned that Ades and colleagues’ paper on the long term health needs of women with a history of sexual trauma might give the impression that most women experience intimate partner violence—physical or sexual—as an isolated event.12 Intimate partner violence is often only one element (albeit the one most easily identified) of a prolonged experience of “intimate terrorism,” where …
Slowing life history (K) can account for increasing micro-innovation rates and GDP growth, but not macro-innovation rates, which declined following the end of the Industrial Revolution
Authors: Michael A. Woodley of Menie, Aurelio José Figueredo, Matthew A. Sarraf
Journal: Behavioral and Brain Sciences (2019)

Abstract Baumard proposes that life history slowing in populations over time is the principal driver of innovation rates. We show that this is only true of micro-innovation rates, which reflect cognitive and economic specialization as an adaptation to high population density, and not macro-innovation rates, which relate more to a population's level of general intelligence.
State‐of‐the‐art in marketed adjuvants and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI)
Authors: Erika Jensen‐Jarolim, Martin F. Bachmann, Sergio Bonini, Lars Jacobsen, Marek Jutel, Ludger Klimek, Vera Mahler, Ralph Mösges, Philippe Moingeon, Robyn E. O´Hehir, Oscar Palomares, Oliver Pfaar, Harald Renz, Claudio Rhyner, Franziska Roth‐Walter, Michael Rudenko, Johannes Savolainen, Carsten B. Schmidt‐Weber, Claudia Traidl‐Hoffmann, Thomas Kündig
Journal: Allergy (2019)

Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)3 ) is the most frequently used adjuvant, with microcrystalline tyrosine (MCT), monophosphoryl lipid A (MPLA) and calcium phosphate (CaP) used less frequently. Recent studies on humans, and using mouse models, have characterized in part the mechanisms of action of adjuvants on pre-existing immune responses. AIT differs from prophylactic vaccines that provoke immunity to infectious agents, as in allergy the patient is presensitized to the antigen. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Contrasting immune effects are seen with different adjuvants. Aluminium hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT redirect the Th2 immune response towards Th1 immunity. After varying lengths of time, each of the adjuvants supports tolerance. Further studies of the mechanisms of action of adjuvants may advise shorter treatment periods than the current three-to-five-year regimens, enhancing patient adherence. Improved lead compounds from the adjuvant pipeline are under development and are explored for their capacity to fill this unmet need.
Shared decision making in cancer care requires better communication and understanding of pathology reports
Authors: Murali Varma, Varsha Shah
Journal: BMJ (2019)

Venhuizen emphasises the importance of patients being involved in management decisions.1 But this requires the patient to be guided by a well informed clinician.

Precision medicine seeks to accurately stratify patients by risk, often with the aid of expensive new tests. Histopathology reports provide critical prognostic information for cancer care, but proven critical histopathological prognostic parameters are not always …
A randomized phase III study of carboplatin plus nab-paclitaxel with or without nintedanib for NSCLC with IPF (J-SONIC)
Authors: K. Otsubo, J. Kishimoto, H. Kenmotsu, Y. Minegishi, H. Horinouchi, T. Kato, E. Ichihara, A. Shiraki, S. Atagi, M. Ando, N. Yamamoto, I. Okamoto
Journal: Annals of Oncology (2019)
A pressure-based single beat method for estimation of right ventricular ejection fraction: proof of concept
Authors: Paul M. Heerdt, Vitaly Kheyfets, Sofia Charania, Ahmed Elassal, Inderjit Singh
Journal: European Respiratory Journal (2019)

The utility of considering right ventricular (RV) contractility and afterload as independent entities and summarising their balance or "coupling" using single beat methods has become widely appreciated [1–3]. Typically expressed as the ratio of end-systolic ventricular elastance (Ees, a load-independent measure of contractility), to arterial elastance (Ea, a lumped parameter measure of afterload) data suggest that when Ees/Ea reaches a critical threshold, the risk of cardiovascular decompensation begins to rise [4]. This proof of concept study suggests that estimation of RV ejection fraction based solely on analysis of the RV pressure waveform may be feasible <http://bit.ly/32ZRoOi> The authors would like to thank Daniel Burkhoff for his insightful comments on fundamental principles of cardiac pressure–volume analysis.
Lncrna Morrbid Regulates Myeloid Cell Survival of AML Driven By a Combination of FLT3ITD and Epigenetic Mutations
Authors: Zhigang Cai, Baskar Ramdas, Jonathan Kotzin, Martin P. Carroll, Gerald Wertheim, Adam Williams, Jorge Henao-Mejia, Reuben Kapur
Journal: Blood (2019)
Preliminary Results from a Phase 1b Study of TAK-079, an Investigational Anti-CD38 Monoclonal Antibody (mAb) in Patients with Relapsed/ Refractory Multiple Myeloma (RRMM)
Authors: Amrita Y. Krishnan, Krina K. Patel, Parameswaran Hari, Sundar Jagannath, Ruben Niesvizky, Rebecca W. Silbermann, Deborah Berg, Jianchang Lin, Eric Robert Fedyk, Antonio Palumbo, Keith E. Stockerl-Goldstein
Journal: Blood (2019)
Genetic dynamics in untreated CLL patients with either stable or progressive disease: a longitudinal study
Authors: Alice Ramassone, Andrea D’Argenio, Angelo Veronese, Alessio Basti, Shimaa Hassan AbdelAziz Soliman, Stefano Volinia, Cristian Bassi, Sara Pagotto, Manuela Ferracin, Laura Lupini, Elena Saccenti, Veronica Balatti, Felice Pepe, Laura Z. Rassenti, Idanna Innocenti, Francesco Autore, Laura Marzetti, Renato Mariani-Costantini, Thomas J. Kipps, Massimo Negrini, Luca Laurenti, Rosa Visone
Journal: Journal of Hematology & Oncology (2019)

Abstract Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome.
Nasal and skin microbiomes are associated with disease severity in paediatric atopic dermatitis Article in press
Authors: Tott‚ J.E.E., L.M. Pardo, K.B. Fieten, M.C. Vos, T.J. van den Broek, F.H.J. Schuren, S.G.M.A. Pasmans
Journal: British Journal of Dermatology (2019)

Background: Alterations of the skin microbiome have been associated with atopic dermatitis (AD) and its severity. The nasal microbiome in relation to AD severity is less well studied. Objectives: We aimed to characterize the nasal and skin microbiomes in children with AD in relation to disease severity. In addition, we explored the differences and correlations between the nasal and skin communities. Methods: We characterized the microbial composition of 90 nasal and 108 lesional skin samples cross-sectionally from patients with AD, using 16S-rRNA sequencing. In addition, a quantitative polymerase chain reaction was performed for Staphylococcus aureus and Staphylococcus epidermidis on the skin samples, and AD severity was estimated using the self-administered Eczema Area and Severity Index. Results: We found an association between the microbial composition and AD severity in both the nose and skin samples (R2 = 2·6%; P = 0·017 and R2 = 7·0%; P = 0·004) (R2 = 2·6%; P = 0·017 and R2 = 7·0%; P = 0·004) strongly driven by staphylococci. However, other species also contributed, such as Moraxella in the nose. Skin lesions were positive for S. aureus in 50% of the children, and the presence and the load of S. aureus were not associated with AD severity. Although the nose and skin harbour distinct microbial communities (n = 48 paired samples; P < 0·001)(n = 48 paired samples; P < 0·001), we found that correlations exist between species in the nose and (other) species on the skin. Conclusions: Our results indicate that both the nasal and the skin microbiomes are associated with AD severity in children and that, next to staphylococci, other species contribute to this association. ? 2019 British Association of Dermatologists
PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation
Authors: Brian T Beaty, Dominic H Moon, Colette J Shen, Robert J Amdur, Jared Weiss, Juneko Grilley-Olson, Shetal Patel, Adam Zanation, Trevor G Hackman, Brian Thorp, Jeffrey M Blumberg, Samip N Patel, Mark C Weissler, Wendell G Yarbrough, Nathan C Sheets, Joel S Parker, D Neil Hayes, Karen E Weck, Lori A Ramkissoon, William M Mendenhall, Roi Dagan, Xianming Tan, Gaorav P Gupta, Bhishamjit S Chera
Journal: JNCI Journal of the National Cancer Institute (2019)

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P = .004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P = .01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT.
Treatment of central and spinal cord neuropathic pain with Scrambler Therapy.
Authors: Thomas J. Smith, David Kamson, Maureen A Mealy, Steve D'Amato
Journal: Journal of Clinical Oncology (2019)

127 Background: Central pain caused by spinal cord or brain injury tends to be severe and refractory despite aggressive treatment, such as in thalamic pain syndrome, neuromyelitis optica spectrum disorder (NMOSD) and other forms of transverse myelitis, and spinal cord gliomas. Methods: We reviewed our experience with treatment of these relatively rare maladies with Scrambler Therapy, a noninvasive form of neuromodulation. Results: One transverse myelitis patient got substantial relief lasting months (Mealy M, Int J MS Care. 201), leading to the NMOSD trial. In a small, sham-controlled randomized trial, NMOSD patient pain scores were reduced in the ST arm from 5 to 1.5 at 30 days, P&lt; 0.01, while the sham treatment gave no relief. (Neurology, resubmitted) Of three patients with pain due to thalamic strokes, surgery and/or radiation, treatment gave over 50% relief long-term in 2 of 3 (D’Amato S, A A Pract. 2018). In the one spinal cord glioma patient, pain in her index finger was reduced from 8-10/10 to 1-2/10 and treatment is ongoing. All successfully treated patients reported marked relief of allodynia and hyperalgesia, in addition to pain relief as reported previously (Marineo G, JPSM 2012). Conclusions: Scrambler therapy is a promising treatment modality for patients with these individually rare but collectively common forms of central pain. It has allowed return to more normal function in most patients, with reductions in pain medication use. Pictures of electrode placement and treatment plans will be shown, allowing others to do this safe and often effective treatment. Clinical trial information: NCT03452176.