Project description:Background and purposeA Thrombolysis in Cerebral Infarction (TICI) score of 3 has been established as therapeutic goal in endovascular therapy (EVT) for acute ischemic stroke; however, in the case of early TICI2b reperfusion, the question remains whether to stop the procedure or to continue in the pursuit of perfection (i.e., TICI 2c/3).MethodsA total of 6635 patients were screened from the German Stroke Registry. Patients who underwent EVT for occlusion of the middle cerebral artery (M1 segment), with final TICI score of 2b/3 were included. Multivariable logistic regression was performed with functional independence (modified Rankin Scale, mRS at day 90 of 0-2) as the dependent variable.ResultsOf 1497 patients, 586 (39.1%) met inclusion criteria with a final TICI score of 2b and 911 (60.9%) with a TICI score of 3. Patients who achieved first-pass TICI3 showed highest odds of functional independence (Odds ratio [OR] 1.71, 95% confidence interval [95% CI] 1.18-2.47). Patients who achieved TICI2b with the second pass (OR 0.53, 95% CI 0.31-0.89) or with three or more passes (OR 0.44, 95% CI 0.27-0.70) had significantly worse clinical outcomes compared to first-pass TICI2b. TICI3 at the second pass was by trend better than first-pass TICI2b (OR 1.55, 95% CI 0.98-2.45), but TICI3 after 3 or more passes (OR 0.93, 95% CI 0.57-1.50) was not significantly different from first-pass TICI2b.ConclusionFirst-pass TICI2b was superior to TICI2b after ≥ 2 retrievals and comparable to TICI3 at ≥ 3 retrievals. The potential benefit in outcome after achieving TICI3 following further retrieval attempts after first-pass TICI2b need to be weighed against the risks.
Project description:Single-cell RNA-seq suffers from unwanted technical variation between cells, caused by its complex experiments and shallow sequencing depths. We present GTestimate a new normalization method based on the Good-Turing estimator, which improves upon conventional methods by accounting for unobserved genes. We validate GTestimate using new ultra-deep sequencing data, generated via a novel cell targeted PCR-amplification approach, and show substantial improvements in cell-cell distance estimation and downstream results.
Project description:Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.
Project description:Direct targeting of oncogenic MYC proteins has been an elusive goal of many cancer drug development efforts. In this issue of Cancer Discovery, Stegmaier and colleagues demonstrate that pharmacologically interfering with the bromodomain and extraterminal (BET) class of proteins potently depletes MYCN in neuroblastoma cells, resulting in cellular cytotoxicity and thus providing a novel approach with a potential impact on a previously undruggable major oncogene.
Project description:Throughout the COVID-19 pandemic, governments and individuals have attempted a wide variety of strategies to limit the damage of the pandemic on human lives, population health, and economies. Contact tracing has been a commonly used strategy, and various approaches have been proposed and attempted. We summarise some methods of contact tracing and testing, considering the resources demanded by each and how features of SARS-CoV-2 transmission affect their effectiveness. We also propose an approach focusing on tracing transmission events, which can be particularly effective when superspreading events play a large role in transmission. Accounting for the best available evidence on a pathogen and for the availability of resources can make control strategies more effective, even if they are not perfect.
Project description:In 2002, Shlaes and Moellering warned that pharmaceutical companies were abandoning antibiotic research and development due to changing regulatory standards regarding noninferiority (NI) clinical trials. NI trials are subject to unique biases that may yield false-positive conclusions. The US Food and Drug Administration (FDA) developed guidance to ensure that NI results truly reflect drug efficacy. These changes, intended to reduce uncertainty in trial results, have shaped trial enrollment and conduct in ways that now require reflection.
Project description:Stigma and isolation are common in people with tuberculosis (TB). Social isolation contributes to reduced health outcomes and TB treatment adherence. Stigma and the drivers of isolation in people with Drug-Resistant (DR)-TB may include modifiable advice and practices of family and Health Care Workers (HCW). This study aimed to understand the drivers of isolation and stigma from the perspective of people with DR-TB in Vietnam. A greater understanding of stigma and isolation is important to identify and balance patients' needs and disease transmission risk. In-depth interviews were conducted with 12 people with DR-TB and seven HCWs who care for people with DR-TB in two provinces in Vietnam. Interviews were audio-recorded, transcribed verbatim and translated to English. Data collection and analysis were conducted simultaneously. The data were then analysed using a thematic framework approach. Stigma and extended isolation were common experiences among people with DR-TB. To mitigate stigma, people with DR-TB used the local term 'lao lực' to describe their condition to others which is believed to be a less infectious and less stigmatising type of TB. This study identified that although HCW informed people with DR-TB of when they were no longer infectious and isolation was no longer required, their infection control advice was not always consistent. Despite knowing they were no longer infectious, most people with DR-TB continued to self-isolate to minimise the perceived repercussions of societal stigma, to protect their 'thể diện' (honour, prestige, reputation), and eliminate all risk of transmitting DR-TB to their family. This study identified three interconnected drivers of self-isolation in Vietnam, including fear of infecting others, fear of stigmatization, and to protect family reputation. TB control programmes need to better understand the social aspects of DR-TB to enable them to better support patients. Educating HCW to provide evidence-based infection control advice is vital.
Project description:More than 50 million cattle are likely exposed to bovine tuberculosis (bTB) worldwide, highlighting an urgent need for bTB control strategies in low- and middle-income countries (LMICs) and other regions where the disease remains endemic and test-and-slaughter approaches are unfeasible. While Bacillus Calmette-Guérin (BCG) was first developed as a vaccine for use in cattle even before its widespread use in humans, its efficacy against bTB remains poorly understood. To address this important knowledge gap, we conducted a systematic review and meta-analysis to determine the direct efficacy of BCG against bTB challenge in cattle, and performed scenario analyses with transmission dynamic models incorporating direct and indirect vaccinal effects ("herd-immunity") to assess potential impact on herd level disease control. The analysis shows a relative risk of infection of 0.75 (95% CI: 0.68, 0.82) in 1,902 vaccinates as compared with 1,667 controls, corresponding to a direct vaccine efficacy of 25% (95% CI: 18, 32). Importantly, scenario analyses considering both direct and indirect effects suggest that disease prevalence could be driven down close to Officially TB-Free (OTF) status (<0.1%), if BCG were introduced in the next 10-year time period in low to moderate (<15%) prevalence settings, and that 50-95% of cumulative cases may be averted over the next 50 years even in high (20-40%) disease burden settings with immediate implementation of BCG vaccination. Taken together, the analyses suggest that BCG vaccination may help accelerate control of bTB in endemic settings, particularly with early implementation in the face of dairy intensification in regions that currently lack effective bTB control programs.