tbuckley/cabot-search huggingface dataset:
A review on current research status of the surface modification of Zn-based biodegradable metals
Authors: Wei Yuan, Dandan Xia, Shuilin Wu, Yufeng Zheng, Zhenpeng Guan, Julietta V. Rau
Journal: Bioactive Materials (2021)

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.
Multicentric EORTC retrospective study shows efficacy of brentuximab vedotin in patients who have mycosis fungoides and Sézary syndrome with variable CD30 positivity*
Authors: E. Papadavid, E. Kapniari, V. Pappa, V. Nikolaou, T. Iliakis, M. Dalamaga, C. Jonak, S. Porkert, S. Engelina, P. Quaglino, P.L. Ortiz‐Romero, C. Vico, A. Cozzio, F. Dimitriou, R. Guiron, E. Guenova, E. Hodak, M. Bagot, J. Scarisbrick
Journal: British Journal of Dermatology (2021)

Brentuximab vedotin (BV) was approved as a therapy for mycosis fungoides (MF) based on the ALCANZA trial. Little real-world data, however, are available.To evaluate the efficacy and safety of BV in patients with MF/Sézary Syndrome (SS) with variable CD30 positivity in a real-world cohort and to explore potential predictors of response.Data from 72 patients with MF/SS across nine EORTC (European Organization for Research and Treatment of Cancer) centres were included. The primary endpoint was to evaluate the proportion of patients with: overall response (ORR), ORR lasting over 4 months (ORR4), time to response (TTR), response duration (RD), progression-free survival (PFS) and time to next treatment (TTNT). Secondary aims included a safety evaluation and the association of clinicopathological features with ORR, RD and TTNT.All 72 patients had received at least one systemic treatment. ORR was achieved in 45 of 67; ORR4 in 28 of 67 with a median TTR of 8 weeks [interquartile range (IQR) 5·5-14] and with a median RD of 9 months (IQR 3·4-14). Median PFS was 7 months (IQR 2-12) and median TTNT was 30 days (6-157·5). Patient response, RD, PFS and TTNT were not associated with any clinicopathological characteristics. In the MF group, patients with stage IIB/III vs. IV achieved longer PFS and had a higher percentage of ORR4. There was a statistically significant association between large-cell transformation and skin ORR (P = 0·03). ORR4 was more frequently achieved in patients without lymph node involvement (P = 0·04).BV is an effective option for patients with MF/SS, including those with variable CD30 positivity, large-cell transformation, SS, longer disease duration and who have been treated previously with several therapies.
Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.
Authors: Silke Gillessen, Ananya Choudhury, Alejo Rodriguez-Vida, Franco Nole, Enrique Gallardo Diaz, Thierry Andre Roumeguere, Gedske Daugaard, Yohann Loriot, Fred Saad, Raymond S. McDermott, Anouk Neven, Beatrice Fournier, Bertrand F. TOMBAL
Journal: Journal of Clinical Oncology (2021)

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]
Interim analysis of IMMUNEBOOST-HPV: A multicenter, randomized, open label, phase II study evaluating the feasibility, and tolerance of neoadjuvant nivolumab in high-risk HPV driven oropharynx cancer.
Authors: Haitham Mirghani, Caroline Even, Alicia Larive, Jerome Fayette, Karen Benezery, Florian Clatot, Lionnel Geoffrois, Yungan Tao, France Nguyen, Emmanuelle Fabiano, Sarah Kreps, Eve Marie Neidhardt, Florence Garic, Anne Auperin, Pierre Blanchard
Journal: Journal of Clinical Oncology (2021)

6037 Background: Among HPV-positive Oropharyngeal Cancer (OPC) patients (pts), some has a less favorable prognosis (T4, N2/N3, smokers &gt;10 pack-year [p/y]). We assume that neoadjuvant immunotherapy might improve their oncological outcomes, so we tested nivolumab (N) prior to ChemoRadiaTion (CRT). Methods: The study population is restricted to HPV positive OPC pts (both p16+ &amp; HPV-DNA+) with advanced disease (T4, N2/N3) or a smoking history &gt;10 p/y. Pts were randomly allocated 1:2 to receive either cisplatin-based CRT (n=20) or 2 cycles of N 240 mg followed by CRT (n=41). The Primary Endpoint (PE) is the rate of pts who can receive Full Treatment in Due Time (FTDT), according to these criteria: a) 2 N infusions on day 1 and on day 14-16 b) CRT started between days 28-37 after the 1st N infusion c) No RT break ≥1 week d) RT dose received &gt;95% of theoretical dose e) Cisplatin dose received ≥200 mg/m² To achieve FTDT, all criteria are required in the Experimental Arm (EA) while only criteria c), d), and e) are required in the Control Arm (CA). In the EA, the trial was designed in 2 steps, with FTDT rate of 88% considered as inacceptable versus an alternative of 98%, a type I error of 0.10, and a type 2 error of 0.08. As per protocol, patient accrual was temporarily suspended after inclusion of 19 pts in the EA (1st step) and results were reviewed by an Independent Data Monitoring Committee (IDMC). To resume pts’ inclusion, FTDT had to be achieved in 18 pts in the EA. Results: From 07/2019 to 09/2020, 30 pts were enrolled including 11 in the CA (demographics are summarized in table). 2 pts in the EA did not reach the PE. For the 1st patient, the cisplatin dose was &lt;200 mg/m 2 due to grade 1 hearing loss and grade 2 tinnitus (1st cycle: 100 mg/m 2 , 2nd cycle: 80 mg/m 2 , no 3rd cycle). For the 2nd patient, CRT began at D38 due to logistical issues (maintenance of RT devices). As this delay was unrelated to N or to patient's condition, the IDMC considered that the inclusions could resume for the 2nd step. 7 N-related Adverse Events (AE) were reported in 4 pts including 3 serious AE (ankylosing spondylitis flare-up, colitis, diabetic ketoacidosis). Conclusions: Neoadjuvant N before CRT seems feasible for the treatment of OPC pts. The trial has reopened to inclusion as recommended by the IDMC. Clinical trial information: NCT03838263. [Table: see text]
Prostaglandin E2 Protects HSC from DNA Damage Induced By Ionizing Radiation By Preventing Generation of Reactive Oxygen Species and Histone Acetylation
Authors: Liqiong Liu, Andrea M Patterson, Hui Lin Chua, Carol Sampson, Artur Plett, Hongge Li, Pratibha Singh, Christie M. Orschell, Louis M. Pelus
Journal: Blood (2017)
Unique Pathogen Peptidomes Facilitate Pathogen-Specific Selection and Specialization of MHC Alleles
Authors: Onur Özer, Tobias L Lenz
Journal: Molecular Biology and Evolution (2021)

A key component of pathogen-specific adaptive immunity in vertebrates is the presentation of pathogen-derived antigenic peptides by major histocompatibility complex (MHC) molecules. The excessive polymorphism observed at MHC genes is widely presumed to result from the need to recognize diverse pathogens, a process called pathogen-driven balancing selection. This process assumes that pathogens differ in their peptidomes-the pool of short peptides derived from the pathogen's proteome-so that different pathogens select for different MHC variants with distinct peptide-binding properties. Here, we tested this assumption in a comprehensive data set of 51.9 Mio peptides, derived from the peptidomes of 36 representative human pathogens. Strikingly, we found that 39.7% of the 630 pairwise comparisons among pathogens yielded not a single shared peptide and only 1.8% of pathogen pairs shared more than 1% of their peptides. Indeed, 98.8% of all peptides were unique to a single pathogen species. Using computational binding prediction to characterize the binding specificities of 321 common human MHC class-I variants, we investigated quantitative differences among MHC variants with regard to binding peptides from distinct pathogens. Our analysis showed signatures of specialization toward specific pathogens especially by MHC variants with narrow peptide-binding repertoires. This supports the hypothesis that such fastidious MHC variants might be maintained in the population because they provide an advantage against particular pathogens. Overall, our results establish a key selection factor for the excessive allelic diversity at MHC genes observed in natural populations and illuminate the evolution of variable peptide-binding repertoires among MHC variants.
Efficacy and safety of toripalimab with anlotinib and chemotherapy as first-line therapy in patients with extensive-stage small-cell lung cancer: Preliminary results of an open-label, single-arm, phase II study.
Authors: Hao Luo, Dan Jian, Yan Feng, Li Zhong, Qian Chen, Wei Guan, Shiheng Zhang, Jiamin Luo, Xueqing Yang, Kan Gong, Yanli Xiong, Mengxia Li, Mingfang Xu, Yu Pu, Liang Zhao, Chengyuan Qian, Nan Dai, Dong Wang
Journal: Journal of Clinical Oncology (2021)

e20570 Background: Although the combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy (EP) is the preferred first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit of the addition of ICIs was still modest. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for normalization the immunosuppressive microenvironment and overcoming the low efficacy of ICIs. We reported the efficacy and safety of toripalimab combined with anlotinib and EP in treatment-naïve ES-SCLC. Methods: The eligible ES-SCLC patients (18-75 years, ECOG PS ≤2), with measurable target lesion (RECIST v1.1) received toripalimab (240 mg, d1) combined with etoposide (100 mg/m 2 , d1-3) plus carboplatin (AUC = 5, d1)/cisplatin (75 mg/m 2 , d1) and anlotinib (12 mg QD, d1-14) of a 21-day cycle for 4-6 cycles, then patients with CR、PR or SD could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 October and 2020 November, 16 treatment-naïve ES-SCLC patients (14 males, 2 females) were enrolled. The median age is 63 (range, 42-74) years. The median follow-up was 7.6 months. 100% (16/16) patients achieved an objective response (1 CR and 15 PR). The DCR was also 100% (16/16). The median DOR had not been reached (range, 4.8+ to 21.9+ month). 37.5% (6/16) patients had disease progression after six months of treatment, while median PFS was not reached. As of Jan 31, 2021, all patients were still alive. The median OS had not been reached. 62.5% (10/16) patients remained on-treatment. The most common adverse events (AEs) were grade 1-2 anemia (75%), decreased appetite (50%) and neutropenia (43.8%). Seven patients had Grade 3 AEs (5 neutropenia; 1 leukopenia, 1 emesis, and 1 ketoacidosis). No Grade 4/5 AEs occurred. Conclusions: Toripalimab combined with anlotinib and etoposide plus carboplatin/cisplatin showed promising anti-tumor activity and tolerable toxicities in treatment-naïve ES-SCLC. Clinical trial information: NCT04731909.
Preliminary results of molecular screening for <i>FGFR</i> alterations (alts) in the RAGNAR histology-agnostic study with the <i>FGFR</i>-inhibitor (FGFRi) erdafitinib.
Authors: Christophe Massard, Shubham Pant, Gopa Iyer, Martin H. Schuler, Olaf Witt, Shukui Qin, Josep Tabernero, Toshihiko Doi, Darren R. Hargrave, Constance Hammond, Shonda Marie Little, Qi Xia, Jing Cao, Ademi E. Santiago-Walker, Hussein Sweiti
Journal: Journal of Clinical Oncology (2021)

4081 Background: FGFR alts (mutations and fusions) have been reported in multiple advanced solid tumors at varying frequencies. These alts may function as oncogenic drivers of disease independent of the underlying tumor type. RAGNAR is an ongoing phase 2, histology-agnostic trial investigating the efficacy and safety of erdafitinib, a selective pan-FGFRi, in patients (pts) with advanced solid tumors and FGFR alts. Little is known about the incidence, diversity or predominant FGFR alts across solid tumors in the clinical setting. Here, we provide an update on molecular screening and enrollment in the primary analysis population. Methods: Pts with advanced solid tumors were molecularly screened for eligible FGFR alts via central next generation sequencing (NGS) or review of local NGS reports. Underlying tumor type, FGFR alts, demographics and key disease characteristics were collected at baseline. Results: From Nov 2019 to Jan 2021, 5758 pts were molecularly screened (central or local) in 15 countries. 191 pts (3.3%) fulfilled primary analysis molecular eligibility criteria; 110 pts were enrolled. Among pts enrolled, 14 (12.7%) had central screening and 96 (87.3%) had local NGS reports. Eligible FGFR alts were identified in 19 tumor types, including rare cancers and ones (eg, pancreatic) with a very low prevalence of FGFR alts in genomic databases (Table). Median age was 57 y, and 19 pts (17.3%) were &lt; 40 y. Gender distribution was even. Conclusions: Findings from molecular screening in the RAGNAR study indicate a wide range of FGFR-altered tumor types, including a notable number of cancers where eligible FGFR alts were considered exceedingly rare (eg, pancreatic). These results demonstrate the feasibility of conducting clinical trials on pts with rare genetic alts by adopting a histology-agnostic design and using both central testing and local NGS reports for molecular screening. This approach also helps investigate rare tumors, where histology-specific trials are challenging. Efficacy and safety results from the RAGNAR study will help define the benefit of erdafitinib in FGFR-altered advanced solid tumors. Clinical trial information: NCT04083976. [Table: see text]
Predictive analytics and tailored interventions improve clinical outcomes in older adults: a randomized controlled trial
Authors: Sara Bersche Golas, Mariana Nikolova-Simons, Ramya Palacholla, Jorn op den Buijs, Gary Garberg, Allison Orenstein, Joseph Kvedar
Journal: npj Digital Medicine (2021)

Abstract This study explored the potential to improve clinical outcomes in patients at risk of moving to the top segment of the cost acuity pyramid. This randomized controlled trial evaluated the impact of a Stepped-Care approach (predictive analytics + tailored nurse-driven interventions) on healthcare utilization among 370 older adult patients enrolled in a homecare management program and using a Personal Emergency Response System. The Control group (CG) received care as usual, while the Intervention group (IG) received Stepped-Care during a 180-day intervention period. The primary outcome, decrease in emergency encounters, was not statistically significant (15%, p = 0.291). However, compared to the CG, the IG had significant reductions in total 90-day readmissions (68%, p = 0.007), patients with 90-day readmissions (76%, p = 0.011), total 180-day readmissions (53%, p = 0.020), and EMS encounters (49%, p = 0.006). Predictive analytics combined with tailored interventions could potentially improve clinical outcomes in older adults, supporting population health management in home or community settings.
Racial and Ethnic Disparities in Cardio-Oncology
Authors: Muhammad Fazal, Jessica Malisa, June-Wha Rhee, Ronald M. Witteles, Fatima Rodriguez
Journal: JACC CardioOncology (2021)

• Racial or ethnic health care disparities in cardio-oncology are present, although data remain sparse. • These disparities stem from structural racism, higher prevalence of CVD risk factors, and reduced access to specialty care. • A multidisciplinary approach is required to dismantle these disparities and should include key stakeholders, including health care policy makers, patients, scientists, and clinicians.
A retrospective analysis examining the use of tissue-based and blood-based NGS in patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Adam Hines, Nausheen Hakim, Kevin Wang, Pratik Shah, Chung-Shien Lee, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2021)

e21195 Background: Next generation sequencing (NGS) of tumor has become an integral part of cancer diagnostics and therapeutics today. While tissue-based (TB) NGS is still considered gold-standard, cell-free DNA NGS obtained from peripheral blood (blood-based or BB) offers many advantages because of its quicker turnaround time, minimally-invasive nature and ability to address tumor heterogeneity and track development of resistance mutations over time. It however does have its disadvantages, predominant of which is its lower sensitivity. Integration of BB and TB NGS can both optimize turnaround time and increase detection of targetable mutations. Methods: We conducted a single institution, IRB approved, retrospective study evaluating NGS testing patterns in patients with advanced NSCLC treated at our institution between 1/1/16 and 3/31/20. Our primary endpoint was to evaluate the number of patients who had BB NGS performed at any point during their clinical course in addition to TB NGS testing. Our secondary endpoint was to evaluate the number of patients for who BB NGS led to change in treatment plan. Exploratory points included the concordance rate between BB and TB NGS performed within 1 month of each other and the details of discordance if any. Results: There was a total of 437 eligible advanced NSCLC patients who were treated at our institution between January 2016 and March 2020. Out of these, 104 (23.8%) had BB NGS performed at some point in their disease course. The median number of BB NGS testing done for these patients was 2 and ranged from 1 to 4. 32/104 (30.8%) of patients had change in management because of BB NGS results. TB and BB NGS were performed within one month of each other in 52 patients. 11 of these (21.2%) had detection of identical actionable mutations (AM) on both BB and TB NGS assays. 5 of the patients (9.6%) had AM detected on TB NGS alone and 6 of the patients (11.5%) had AM detected on BB NGS alone. 30/52 patients (57.7%) had no AM identified on both BB and TB NGS. Conclusions: BB NGS has added tremendous value to diagnosis and treatment of NSCLC. It is increasingly used in practice, in tandem with TB NGS. Nearly a fourth of our patients had BB NGS performed at some point in their clinical course. Nearly 20% of simultaneously performed BB and TB NGS were discordant and an AM was identified in only one of the biopsies. Although further research is needed, our study supports simultaneous BB and TB testing at diagnosis and progression thereby maximizing therapeutic potential.
R-scale for pulmonary fibrosis: a simple, visual tool for the assessment of health-related quality of life
Authors: Ciaran Scallan, Lauren Strand, Jennifer Hayes, Suha Kadura, Bridget Collins, Lawrence Ho, Carolyn Spada, Will Canestaro, Martin Kolb, Ganesh Raghu
Journal: European Respiratory Journal (2021)

Patients with idiopathic pulmonary fibrosis (IPF) experience impaired health-related quality of life (HRQoL). Several tools have been developed to objectively assess HRQoL in this patient population, but none are in use in routine clinical practice.To develop a rapid, specific tool that can be used for patients with IPF during routine clinic visits.A novel and simple five-item numerical rating scale was developed and compared with two other previously validated tools. 100 consecutive patients with IPF managed at a centre for interstitial lung disease were recruited to complete the Raghu scale for pulmonary fibrosis (R-Scale-PF), King's Brief Interstitial Lung Disease questionnaire (K-BILD), and the EuroQol Five-Dimensional Five-Level questionnaire (EQ-5D-5L) in addition to pulmonary function and 6-min walk tests.All 100 patients successfully completed the three HRQoL tools with 53 completing them again at follow-up visits. Internal consistency was high (Cronbach's α 0.825) with minimal floor/ceiling effect. Concurrent validity of the R-Scale-PF was moderate to high compared with the K-BILD (r=-0.713) and the EQ-5D-5L (r=-0.665). Concurrent validity was moderate with physiologic measures (forced vital capacity, r=-0.307, 6-min walking distance, r=-0.383). The R-Scale-PF demonstrated good known-groups validity when comparing scores across stages of disease severity.The R-Scale-PF correlates well with the K-BILD and EQ-5D-5L. It is hoped that this novel simple numerical rating scale tool, subject to validation in patients from other centres, will provide an opportunity to objectively measure HRQoL in routine clinical practice for patients with IPF.