tbuckley/cabot-search huggingface dataset:
ZORO: A prospective randomized multicenter study to prevent chemotherapy-induced ovarian failure with the GnRH-agonist goserelin in young hormone-insensitive breast cancer patients receiving anthracycline containing (neo-) adjuvant chemotherapy (GBG 37)
Authors: B. Gerber, H. Stehle, F. Ricardo, N. Maass, D. Fischer, H. L. Sommer, B. Conrad, K. Mehta, S. Loibl
Journal: Journal of Clinical Oncology (2009)

526 Background: Premature ovarian failure due to chemotherapy leads to premature menopause and infertility. To prevent related health problems and to maintain fertility after chemotherapy in patients with hormone insensitive breast cancer, ovarian function might be protected by using a GnRH-agonist. Methods: Patients (pts) &lt; 46 years, with a hormone insensitive breast cancer were randomized to receive an anthracycline/taxane containing chemotherapy with or without goserelin 3.6mg in parallel as subcutaneous injection in the abdominal wall starting at least 2 weeks before chemotherapy, and thereafter every 4 weeks (28 ± 3 days) until the end of the last chemotherapy cycle (EOC). Primary objective is the ovarian function 6 months after EOC. The endpoint normal ovarian function 6 months after EOC is defined by two consecutive menstrual periods within 21–35 days within a time frame of 5–8 months after last application of goserelin. Secondary objectives are treatment compliance, toxicity, quality of life; menopausal symptoms score; ovarian function at 0, 6, 12, 18, and 24 months by menstruation and endocrine function (estradiol, progesterone, FSH, LH, SHBG), duration until recovery of regular menstrual period, pregnancy rate. Results: Between March 2005 and August 2007, 63 pts in16 sites were enrolled. 60 are considered to be evaluable, 3 pts withdrew their informed consent. Nine serious adverse events occurred, which were mainly chemotherapy related and had no relationship to goserelin (3 febrile neutropenias, 2 neutropenias, 2 nauseas, 1 infection of port-catheter, and 1 psychogenic hyperventilation). No treatment related deaths occurred. Two women became pregnant, one in each group. Conclusions: There have been no risks identified related to the safety of the ZORO trial. The treatment with goserelin is feasible in all pts with acceptable hematological and non-hematological tolerability. Final efficacy analysis will be presented at the Meeting. [Table: see text]
FDG PET/CT Findings in Biliary Papillomatosis
Authors: Zhuolong Tu, Yingnan Yang, Jing Ruan, Jinfu Tu
Journal: Clinical Nuclear Medicine (2020)

Abstract Biliary papillomatosis is a rare disease with high malignant potential. A 64-year-old woman underwent FDG PET/CT, which showed an intense FDG uptake in the location of an aggregated biliary papillomatosis with high-grade intraepithelial neoplasia/carcinoma in situ but did not show FDG uptake in the sporadic, small biliary papilloma. FDG PET/CT may be an effective method to identify the components of the malignant transformation of biliary papillomatosis.
Assessment of Pediatric Outpatient Visits for Notifiable Infectious Diseases in a University Hospital in Beijing During COVID-19
Authors: Zujin Luo, Shunli Li, Nan Li, Yichong Li, Ying Zhang, Zhixin Cao, Yingmin Ma
Journal: JAMA Network Open (2020)

This cross-sectional study assesses changes in numbers of pediatric outpatient visits for notifiable infectious diseases acquired through droplet transmission, contact transmission, or both after implementation of coronavirus disease 2019 (COVID-19)–related public health measures during the COVID-19 outbreak in Beijing, China.
Performance of lipid fingerprint-based MALDI-ToF for the diagnosis of mycobacterial infections
Authors: Ximena Gonzalo, Agnieszka Broda, Francis Drobniewski, Gerald Larrouy-Maumus
Journal: Clinical Microbiology and Infection (2020)

Bacterial diagnosis of mycobacteria is often challenging because of the variability of the sensitivity and specificity of the assay used, and it can be expensive to perform accurately. Although matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has become the workhorse of clinical laboratories, the current MALDI methodology (which is based on cytosolic protein profiling) for mycobacteria is still challenging due to the number of steps involved (up to seven) and potential biosafety concerns. Knowing that mycobacteria produce surface-exposed species-specific lipids, we here hypothesized that the detection of those molecules could offer a rapid, reproducible and robust method for mycobacterial identification.We evaluated the performance of an alternative methodology based on characterized species-specific lipid profiling of intact bacteria, without any sample preparation, by MALDI MS; it uses MALDI-time-of-flight (ToF) MS combined with a specific matrix (super-2,5-dihydroxybenzoic acid solubilized in an apolar solvent system) to analyse lipids of intact heat-inactivated mycobacteria. Cultured mycobacteria are heat-inactivated and loaded directly onto the MALDI target followed by addition of the matrix. Acquisition of the data is done in both positive and negative ion modes. Blinded studies were performed using 273 mycobacterial strains comprising both the Mycobacterium tuberculosis (Mtb) complex and non-tuberculous mycobacteria (NTMs) subcultured in Middlebrook 7H9 media supplemented with 10% OADC (oleic acid/dextrose/catalase) growth supplement and incubated for up to 2 weeks at 37°C.The method we have developed is fast (<10 mins) and highly sensitive (<1000 bacteria required); 96.7% of the Mtb complex strains (204/211) were correctly assigned as MTB complex and 91.7% (22/24) NTM species were correctly assigned based only on intact bacteria species-specific lipid profiling by MALDI-ToF MS.Intact bacterial lipid profiling provides a biosafe and unique route for rapid and accurate mycobacterial identification.
Progression-free survival in intention to treat populations versus total KRAS populations in patients treated for metastatic colorectal cancer: A pooled review
Authors: B. A. Costello, J. R. Hecht, A. Grothey
Journal: Journal of Clinical Oncology (2009)

4054 Background: In treatment trials of patients with metastatic colorectal cancer (mCRC), KRAS mutation status of tumor samples has been retrospectively demonstrated to be predictive of treatment benefit. Historically, clinical trials have not required tissue samples to be tested for KRAS mutation status as a condition of enrollment. Therefore, KRAS analyses have been based on available tissue samples representing only a portion of patients retrospectively analyzed for KRAS status and correlated with treatment end- points. Methods: A weighted analysis of pooled data was performed using six recently presented or published clinical trials of targeted therapy in mCRC which tested for the association of KRAS status with Progression Free Survival (PFS). The goal of the analysis was to determine whether there is a significant difference in PFS between the intention to treat (ITT) population and KRAS population in both the treatment and control arms. Results: The total ITT population of the pooled studies is 3864, and for the total KRAS population, 2295; a 59.4% retrieval rate (range 28–92%) for tissue samples available for KRAS analysis. The weighted Δ PFS across all arms between the ITT population and the KRAS population was 0.2 months with a range of 0–0.7 months. Of the 12 subgroups (6 control and 6 treatment arms), five had no difference in PFS between ITT and KRAS evaluable populations at all, and two additional subgroups demonstrated a difference PFS of only 0.1 months. The two studies with the lowest tissue retrieval rates (28% and 45%) had the largest Δ PFS. Conclusions: There is no meaningful difference in the PFS between the ITT and KRAS populations based on our analysis of pooled data. The difference in PFS was greatest in the two studies with the lowest rate of retrieval of tissue samples for KRAS testing. As such, subgroup analysis is better able to estimate and reflect the ITT population if a higher percentage of samples is able to be obtained. Further, our results suggest that there is not an inherent systemic bias influencing any potentially observed differences in PFS. Tissue samples should be required for all patients entering a clinical trial to avoid this issue and to make retrospective analysis more valid. [Table: see text]
Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Authors: M. Mohebtash, R. A. Madan, P. M. Arlen, M. Rauckhorst, K. Y. Tsang, V. Cereda, M. Vergati, D. J. Poole, W. L. Dahut, J. Schlom, J. L. Gulley
Journal: Journal of Clinical Oncology (2009)

5144 Background: There are few treatment options for mCRPC pts. Immunotherapy + adjuvant immunomodulators is a promising modality. PSA-TRICOM V is composed of poxviral vectors encoding PSA and 3 costimulatory molecules (ICAM-I, LFA-3, and B7.1) and has clinical activity in mCRPC. Ipi blocks CTLA-4, a T-cell downregulatory receptor, has clinical activity in mCRPC as monotherapy and has also been shown to enhance anti-tumor responses in combination with V in preclinical studies. Methods: Pts received V and GM-CSF q 4 weeks in 4 sequential cohorts of escalating doses of ipi at 1, 3, 5, and 10 mg/kg (DL1–4 respectively). After 6 courses of ipi, pts could receive a maintenance dose q 3 months (mo) until progression. Results: Study accrual is complete with 30 pts. There was no DLT and no &gt; G2 adverse event (AE) attributed to V. There were 20 ≥ G2 immune-related AE (irAE): 0/3, 2/6, 5/6 and 13/15 pts on DL1–4, respectively. There was no evidence of clinical benefit in the 6 pts who had prior chemo on DL1 and 2, so subsequently we excluded pts with prior chemo. Median TTP for 9 chemo-naïve pts treated on DL2 and 3 was 6.1 mo (2.9–11.6 mo). Median PSA doubling time (DT) ↑ from 2.2 mo at baseline to 3.7 on study (p = 0.17). 5 of 9 had ≥ 50% ↓ in PSA from peak during study and 1 had a sustained ↓ PSA &gt; 95% from baseline. 4 of these pts had stable disease (SD) for ≥ 6 mo and 2 had unconfirmed partial responses by RECIST. Of the 15 pts on DL4, to date 9 have had SD for ≥ 6 mo (2 ≥ 12 mo); 4 remain on trial. 1 had a sustained ↓ in PSA &gt; 99% from baseline and is still on study after 12 mo. Median PSA DT ↑ &gt; 3-fold from 2.6 mo at baseline to 8.2 on study (p = 0.01) in DL4. The 24 chemo-naïve pts had PSA DT ↑ from 2.5 to 6 mo (p = 0.003). 14 of 30 pts had a PSA ↓ from baseline or peak PSA on study. 2 of 14 had no irAE, 12 showed ≥ G2 irAE temporally associated with PSA ↓. 5 of 9 pts had &gt; 2–5 fold ↑ in T-cell responses by ELISPOT assay and 4 of 13 had significant ↓ in their IL-6 levels. Immune responses appeared to correlate with clinical activity. Conclusions: This combination has clinical activity in pts with chemo-naïve mCRPC and seems to correlate with immune responses. It is associated with manageable side effects; however, further studies are required to see if the combination is more effective than either agent alone. No significant financial relationships to disclose.
Randomized phase III trials of standard chemotherapy with or without targeted agents as first-line therapy in non-small cell lung cancer
Authors: T. Hoang
Journal: Journal of Clinical Oncology (2009)

e19092 Purpose: To characterize the pattern and outcome of randomized phase III trials involving standard chemotherapy with/without novel agents as first-line treatment in advanced NSCLC patients (pts). Methods: The trials included in this analysis were identified through a search of MEDLINE as well as websites (ASCO, IASLC) and meeting proceedings. Studies comparing novel agents alone to standard regimens were excluded. Results: Of 20 identified trials (16,050 pts), 11 (8,647 pts) were published between 2004–2008, and 9 (7,403 pts) were reported at scientific meetings (mostly between 2005–2008), but have not been published yet. All studies were conducted within the last 10 years. Majority were industry-sponsored studies; 4 (20%) were conducted by cooperative or non-profit groups. Chemotherapy chosen as the standard regimens involved cisplatin or carboplatin in combination with a third-generation drug with paclitaxel (10 trials) and gemcitabine (6 trials) being the most common drugs. The experimental drugs included agents with different molecular targets (EGFR, VEGF, MMP, PKC, FTI, TLR-9¼). Overall survival was primary endpoint in all 11 published studies. PFS was chosen as primary in 2 non-published studies. When comparing the standard arms (chemotherapy alone) across the 11 published trials, there was a large difference in term of response rate RR (15% to 47%), while survival endpoints showed a smaller difference (median overall survival OS 9–10.9 months; progression free survival PFS 4.5–5.5 months; and time to progression TTP 4.9–6 months). Among 11 published studies, only one showed positive result with a consistency in all endpoints (OS, PFS and RR). Of 9 non-published studies, 2 studies were reported as positive by the investigators, although preliminary results of primary and secondary endpoints were somewhat inconsistent. Conclusions: Within the last decade, 20 randomized phase III trials involving a large number of chemo-naïve NSCLC patients were conducted. There was a variation in eligibility and patient characteristics, study design (primary endpoints) as well as results among the studies. No significant financial relationships to disclose.
Tuning parameters of dimensionality reduction methods for single-cell RNA-seq analysis
Authors: Felix Raimundo, Celine Vallot, Jean-Philippe Vert
Journal: Genome biology (2020)

Many computational methods have been developed recently to analyze single-cell RNA-seq (scRNA-seq) data. Several benchmark studies have compared these methods on their ability for dimensionality reduction, clustering, or differential analysis, often relying on default parameters. Yet, given the biological diversity of scRNA-seq datasets, parameter tuning might be essential for the optimal usage of methods, and determining how to tune parameters remains an unmet need.Here, we propose a benchmark to assess the performance of five methods, systematically varying their tunable parameters, for dimension reduction of scRNA-seq data, a common first step to many downstream applications such as cell type identification or trajectory inference. We run a total of 1.5 million experiments to assess the influence of parameter changes on the performance of each method, and propose two strategies to automatically tune parameters for methods that need it.We find that principal component analysis (PCA)-based methods like scran and Seurat are competitive with default parameters but do not benefit much from parameter tuning, while more complex models like ZinbWave, DCA, and scVI can reach better performance but after parameter tuning.
Regarding the role of <i>F</i><sub>ENO</sub> in predicting failure after ICS reduction in mild-to-moderate asthma patients
Authors: Luis Pérez de Llano, Nagore Blanco Cid, Irene Martin Robles, Rafael Golpe, Olalla Castro-Añon, David Dacal Rivas
Journal: European Respiratory Journal (2020)

Although exhaled nitric oxide fraction ( F ENO) is one of most widely used type-2 biomarkers, there remains some controversy about its role in diagnosing asthma, assessing adherence, predicting steroid responsiveness and preventing exacerbations by adjusting medication dosage. Thus, we read with great interest the well-conducted individual patient data meta-analysis by Wang et al . [1]. The study showed that the use of F ENO can potentially assist clinicians in deciding whether to reduce inhaled corticosteroid (ICS) dose in well-controlled asthmatics. We appreciate the authors' efforts in illuminating this important topic, but there is an essential methodological consideration that must be taken into account, which has already been outlined by Dinh-Xuan and Brusselle [2] in their editorial and by the authors themselves: the study did not evaluate the impact of other potential risk factors for exacerbations. We must be cautious in deciding whether or not to reduce ICS dose based only on the measurement of F ENO <https://bit.ly/2VAHLVu>
Enhancing the Injectability of High Concentration Drug Formulations Using Core Annular Flows
Authors: Vishnu Jayaprakash, Maxime Costalonga, Somayajulu Dhulipala, Kripa K. Varanasi
Journal: Advanced Healthcare Materials (2020)

Abstract Highly concentrated biological drug formulations would offer tremendous benefits to global health, yet they cannot be manually injected using commercial syringes and needles due to their high viscosities. Current approaches to address this problem face several challenges such as crosscontamination, high cost, needle clogging, and protein inactivation. This work reports a simple method to enhance formulation injectability using a core annular flow, where the transport of highly viscous fluids through a needle is enabled by coaxial lubrication by a less viscous fluid. A phase diagram to ensure optimally lubricated flow while minimizing the volume fraction of lubricant injected is established. The technique presented here allows for up to a 7x reduction in injection force for the highest viscosity ratio tested. The role of buoyancy‐driven eccentricity in governing nominal pressure reduction is also examined. Finally, the findings are implemented into the development of a double barreled syringe that significantly expands the range of injectable concentrations of several biologic formulations.
Cetuximab in combination with chemoradiotherapy prior to surgery in patients with resectable, locally advanced esophageal carcinoma: A prospective, multicenter phase lb-ll trial of the Swiss Group for Clinical Cancer Research (SAKK 75/06)
Authors: T. Ruhstaller, M. Pless, J. C. Schuller, H. Kranzbühler, R. von Moos, P. Moosmann, D. Rauch, M. Montemurro, P. M. Schneider, V. Hess
Journal: Journal of Clinical Oncology (2009)

4570 Background: Cetuximab significantly enhances efficacy of radiotherapy and chemotherapy in head and neck cancer. We investigated the safety and feasibility of adding cetuximab to neoadjuvant chemoradiation of locally advanced esophageal cancer. Methods: Pts with resectable, locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (staged by EUS, CT and PET scan) were treated with 2 cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2 q3w and weekly cetuximab 250mg/m2), followed by concomitant chemo- immuno-radiation therapy (CIRT: docetaxel 20mg/m2, cisplatin 25mg/m2 and cetuximab 250mg/m2 weekly five times concomitant with 45 Gy radiotherapy in 25 fractions); followed by surgery 4–8 weeks later. The phase I part consisted of 2 cohorts of 7 patients each, without and with docetaxel during CIRT, respectively. Interpatient dose-escalation (adding docetaxel during CIRT) was possible if &lt; 2 out of 7 pts of the 1 st cohort experienced limiting toxicity. Having finished the phase 1 part, 13 additional patients were treated with docetaxel-containing CIRT in a phase II part. Pathological response was evaluated according to the Mandard classification. Results: 27 pts from 12 institutions were included. As of today, results from 20 pts are available (cohort 1: 7, cohort 2: 7, phase ll : 6). Median age was 64yrs (range 47–71). 11 AC; 9 SCC. 19 pts (95%) completed CIRT (1 pt stopped treatment during induction therapy due to sepsis). 17 pts underwent resection (no surgery: 1pt for PD, 1pt for cardiac reasons). Grade 3 toxicities during CIRT included anorexia 15%, dysphagia/esophagitis 15%, fatigue 10%, nausea 10%, pruritus 5%, dehydration 5%, nail changes 5% and rash 5% .1 pt suffered from pulmonary embolism. 13 pts (65%, intention-to-treat) showed a complete or near complete pathological remission (cohort 1: 5, cohort 2: 4, phase II: 4). Conclusions: Adding cetuximab to preoperative chemoradiation for esophageal cancer is safe and feasible in a community-based multicenter setting. Antineoplastic activity is encouraging with 65% pathological responders. [Table: see text]
Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae
Authors: Desen Sun, Rongpan Bai, Wei Zhou, Zhengrong Yao, Yaxin Liu, Shasha Tang, Xiaolong Ge, Liang Luo, Chi Luo, Guo-fu Hu, Jinghao Sheng, Zhengping Xu
Journal: Gut (2020)

Objective Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD. Design The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples. Results ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1 -deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients. Conclusion These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.
SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2
Authors: Lisa von Wenserski, Christoph Schultheiß, Sarah Bolz, Simon Schliffke, Donjete Simnica, Edith Willscher, Helwe Gerull, Gerrit Wolters-Eisfeld, Kristoffer Riecken, Boris Fehse, Marcus Altfeld, Peter Nollau, Mascha Binder
Journal: Leukemia (2020)

Abstract We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play a role in NK cell biology, we reasoned that these receptors may impact NK cell-mediated CLL immunity. Indeed, our experiments showed significantly decreased degranulation capacity of primary NK cells from CLL patients expressing low levels of SLAMF1 and SLAMF7. Since the SLAMF low signature was strongly associated with an unmutated CLL immunoglobulin heavy chain (IGHV) status in large datasets, we investigated the impact of SLAMF1 and SLAMF7 on the B cell receptor (BCR) signaling axis. Overexpression of SLAMF1 or SLAMF7 in IGHV mutated CLL cell models resulted in reduced proliferation and impaired responses to BCR ligation, whereas the knockout of both receptors showed opposing effects and increased sensitivity toward inhibition of components of the BCR pathway. Detailed molecular analyzes showed that SLAMF1 and SLAMF7 receptors mediate their BCR pathway antagonistic effects via recruitment of prohibitin-2 (PHB2) thereby impairing its role in signal transduction downstream the IGHV-mutant IgM-BCR. Together, our data indicate that SLAMF receptors are important modulators of the BCR signaling axis and may improve immune control in CLL by interference with NK cells.