Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas

The levels of cell free circulating tumor DNA (ctDNA) in plasma correlate with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variant-specific droplet digital polymerase chain reaction was designed for each mutation. At time of enrollment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2 out of 6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in one patient with CNS lymphoma in complete remission and in one patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed, indicating that CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in two cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though no tumoral cells were observed by flow cytometry (FC), indicating that CSF ctDNA detected residual disease better than FC. In conclusion, CSF ctDNA can detect CNS lesions better than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas

Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial

Background Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor VIII (FVIII) expression and provides bleed protection. Objectives Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years post-treatment. Methods In the phase 3 GENEr8-1 trial, 134 adult males with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6x1013 vg/kg infusion of valoctocogene roxaparvovec. Efficacy endpoints included annualized bleed rate (ABR), annualized FVIII infusion rate, FVIII activity, and the Haemophilia-Specific Quality of Life Questionnaire for Adults (Haemo-QOL-A). Adverse events (AEs) and immunosuppressant use were assessed. Change from baseline was assessed after participants discontinued prophylaxis (scheduled for week 4). Results Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated ABR (−82.6%; P<0.0001) and annualized FVIII infusion rate (−95.5%; P<0.0001) were maintained from previous years in the primary analysis population of 112 participants who enrolled from a noninterventional study. During year 4, 81/110 rollover participants experienced 0 treated bleeds. Week 208 mean and median chromogenic FVIII activity were 16.1 IU/dL and 6.7 IU/dL, respectively, in 130 modified intention-to-treat (mITT) participants. Seven participants resumed prophylaxis since the previous data cutoff. Mean change from baseline to week 208 in Haemo-QOL-A Total Score (P<0.0001) remained clinically meaningful for mITT participants. Alanine aminotransferase elevation was the most common AE during year 4 (56/131 participants); none required immunosuppressants. Conclusions Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with no new safety signals

Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas

Limfoma no Hodgkin agressiu; Limfoma del SNCLinfoma no Hodgkin agresivo; Linfoma del SNCAggressive Non-Hodgkin's Lymphoma; CNS lymphomaThe levels of cell free circulating tumor DNA (ctDNA) in plasma correlated with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variant-specific droplet digital PCR was designed for each mutation. At time of enrolment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2/6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in 1 patient with CNS lymphoma in complete remission and in 1 patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed; indicating CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in 2 cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though a complete decrease in CSF tumor cells was observed by flow cytometry (FC), indicating CSF ctDNA better detected residual disease than FC. In conclusion, CSF ctDNA can better detect CNS lesions than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas.This work was supported by research funding from Fundación Asociación Española contra el Cáncer (AECC) (to JS, MC and PA); FERO (to JS), laCaixa (to JS), BBVA (CAIMI) (to JS), the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias (PI16/01278 to JS; PI17/00950 to MC; PI17/00943 to FB) cofinanced by the European Regional Development Fund (ERDF) and Gilead Fellowships (GLD16/00144, GLD18/00047, to FB). MC holds a contract from Ministerio de Ciencia, Innovación y Universidades (RYC-2012-12018). SB received funding from Fundación Alfonso Martin Escudero. LE received funding from the Juan de la Cierva fellowship. We thank CERCA Programme / Generalitat de Catalunya for institutional support

Raising Awareness on Contract Cheating -Lessons Learned from Running Campus-Wide Campaigns

Contract cheating is a growing menace that most academic institutions are grappling with globally. With governments now taking steps to help combat the industry and ban such services, it is also important to encourage students to stay away from such services through proactive strategies to raise awareness so that students stop using such services. This paper uses a case study approach to capture a time-series data from three years of a university campus\u27s efforts to raise awareness by celebrating the International Centre for Academic Integrity (ICAI)\u27s International Day of Action Against Contract Cheating. This is in order to explore if such campaigns can be used as tools to increase student understanding of contract cheating as an academic misconduct issue and what roles students can play in raising awareness among other students on contract cheating. Proposing to look at contract cheating as a social issue, the paper positions the misconduct as such and explores how awareness campaigns can help address contract cheating. Over the three years, results show steep increase in awareness of contract cheating, a type of academic misconduct, and that students themselves have a positive influence on other students when raising awareness. An interesting finding of the study is that graduated students have had an impact by showing responsibility to younger students and by actively denouncing contract cheating companies and their approaches on social media; thus providing solid evidence that awareness campaigns can help increase awareness which is the first step towards building a culture of integrity in any campus

EFFECT OF ALLOXAN TOXICITY ON THE GLYCOGEN CONTENT OF LIVER AND PANCREAS INSWISS ALBINO MICE

Alloxan is a diabetogenic agent. The pancreas and liver are found to be the major sites for its absorption in Swiss albino mice. It affects the production of insulin by damaging 3 cells of the pancreas. Insulin deficiency results in impairment of carbohydrate metabolism, resulting in hyperglycemic condition

Whose work is it anyway? Exploring the existence of contract cheating in the UAE context

Academic integrity is the foundation upon which the academic sector stands. Contract cheating, a form of academic dishonesty where students get assessments written by others, has taken on a darker turn with the ease of use and over-reliance on technology. To the best of the researchers\u27 knowledge, no studies so far have looked at the student population and trends in contract cheating in the UAE (United Arab Emirates), a country whose education sector has been booming in recent years. Therefore, it is imperative to explore and understand the contract cheating phenomenon in the UAE. For this preliminary study, focus group interviews were conducted with undergraduate students. The results indicated that 95% of students were aware of contract cheating, 91% aware of others receiving substantial, unpermitted help, and 77% were aware of others turning in work done by others. These findings document the first records of student-reported incidences and establish the existence of contract cheating in the UAE. With this knowledge, the paper paves the way for a comprehensive future study with a larger dataset of instances in the UAE

Preliminary Review - Universities\u27 Open Source Academic Integrity Policies in the UAE

In this paper, we conducted investigation of the state of academic integrity policies in universities accredited by the UAE Ministry of Higher Education. For practical reasons, we focused on universities whose websites provided an open access to their policies of academic integrity. The accessible policies were collected, then assessed based on eight identified categories mapped to the five core elements as defined by the Academic Integrity Standards Project conducted in Australia. This project found that of the seven universities whose policies were available as open access online from sample population, highlighted disparities including unclear purpose of the policy, missing complete definitions of academic integrity, misconducts, reporting systems and so on. These findings lay the foundation for a more comprehensive review and analysis of all the universities\u27 policies, not only those with open-access policies to assist stakeholders in developing shared understanding of academic integrity across all institutions in the country

Long-term efmoroctocog alfa prophylaxis improves perceived pain, mental, and physical health in patients with hemophilia A: analysis of phase III trials using patient-reported outcomes

Background: Hemophilia-associated bleeding and resultant joint pain and mobility restrictions can predispose patients to poor health-related quality of life (HRQoL). Therefore, efficacy of a treatment needs to address more than just annualized bleed rates. Objectives: Describe the evolution of HRQoL, pain, and activity in patients with hemophilia A, treated with efmoroctocog alfa prophylaxis. Design: A post hoc analysis from Kids A-LONG (NCT01458106), A-LONG (NCT01181128), and long-term extension study ASPIRE (NCT01454739) assessed change in pain and activity-related patient-reported outcomes (PROs). Methods: Physical health, pain, and HRQoL were assessed by PROs for a cumulative treatment duration of up to ~6 years. The primary endpoint was change from baseline in EuroQoL (EQ)-5D and Haemophilia Quality of Life Questionnaire (Haem-A-QoL). Results: 118 adult/adolescents and 71 pediatric patients were included. The proportion of adults and adolescents reporting no problem in the EQ-5D analysis of ‘ pain/discomfort ’ significantly increased from A-LONG baseline (35.04%; 41/117) to ASPIRE month 30 (44.68%; 21/47; p  = 0.024). Mean (standard deviation) Haem-A-QoL subdomain scores for ‘ feeling ’ and ‘ physical health ’ at A-LONG baseline improved by −3.24 (15.13; p  = 0.018) and −3.85 (23.07; p  = 0.047), respectively, at study end. Proportion of pediatric patients reporting no problem on the EQ-5D analysis of ‘ pain/discomfort ’, significantly increased from A-LONG baseline (75.0%; 42/56) to ASPIRE baseline (95.56%; 43/45; p  = 0.046). Satisfaction levels for pediatric patients were high at A-LONG baseline and maintained until study end. Conclusion: Long-term efmoroctocog alfa prophylaxis reduces pain and improves HRQoL in adult and adolescent patients with hemophilia A. In pediatric patients, it reduces perceived pain and maintains satisfaction levels. Trial registration: NCT01458106, NCT01181128, NCT01454739