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Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

Cases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle‐associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first‐line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T‐cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future. Cancer immunotherapies are emerging as one of the main faces in the new era of cancer treatment and personalised medicine. The cancer immunotherapy pharmaceutical industry is now worth billions of dollars and much research is now focused on harnessing their huge potential in treating a wide range of diseases. In this review, we discuss the different types of cancer immunotherapies currently licensed and in development for the treatment of hepatocellular carcinoma, their drawbacks and limitations, and future innovations that are currently being researched in order to maximise their effectiveness for use in clinical practice.

People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3–6 months after the second dose in the cancer cohort and control population. The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8–69·9) in the control population and 65·5% (65·1–65·9) in the cancer cohort. Vaccine effectiveness at 3–6 months was lower in the cancer cohort (47·0%, 46·3–47·6) than in the control population (61·4%, 61·4–61·5). COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10 T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10 T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10 T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10 T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies

Real-time biofeedback is a promising post-stroke gait rehabilitation strategy that can target specific gait deficits preferentially in the paretic leg. Our previous work demonstrated that the use of an audiovisual biofeedback interface designed to increase paretic leg propulsion, measured via anterior ground reaction force (AGRF) generation during late stance phase of gait, can induce improvements in peak AGRF production of the targeted and paretic limb of able-bodied and post-stroke individuals, respectively. However, whether different modes of biofeedback, such as visual, auditory, or a combination of both, have differential effects on AGRF generation is unknown. The present study investigated the effects of audio only, visual only, or audiovisual AGRF biofeedback in able-bodied and post-stroke individuals. Seven able-bodied (6 females, 27 ± 2 years) and nine post-stroke individuals (6 females, 54 ± 12 years, 42 ± 26 months post-stroke) completed four 30-s walking trials on a treadmill under 4 conditions: no biofeedback, audio biofeedback, visual biofeedback, or audiovisual biofeedback. Compared to walking without biofeedback, all three biofeedback modes significantly increased peak AGRF in the targeted and paretic leg. There was no significant difference in peak AGRF between the three biofeedback modes. Able-bodied individuals demonstrated greater feedback-induced increase in stride-to-stride variation of AGRF generation during audio biofeedback compared to visual biofeedback; however, similar results were not observed in the post-stroke group. The present findings may inform future development of real-time gait biofeedback interfaces for use in clinical or community environments.

Immunization against common bacterial and viral diseases has helped prevent millions of deaths worldwide. More recently, the concept of vaccination has been developed into a potentially novel strategy to treat and prevent cancer formation, progression, and spread. Over the past few years, a handful of anti-cancer vaccines have been licensed and approved for use in clinical practice, thus providing a breakthrough in the field. However, the path has not always been easy, with many hurdles that have had to be overcome in order to reach this point. Nevertheless, with more anti-cancer vaccines currently in development, there is still hope that they can eventually become routine tools used in the treatment and prevention of cancer in the future. This review will discuss in detail both types of anti-cancer vaccine presently used in clinical practice - therapeutic and preventive - before considering some of the more promising anti-cancer vaccines that are currently in development. Finally, the issue of side effects and the debate surrounding the overall cost-effectiveness of anti-cancer vaccines will be examined.

High-intensity readmill training (FAST) and functional electrical stimulation (FES) are both evidence-supported interventions that improve gait function post-stroke, but their neural mechanisms are unclear. Here, we tested the hypothesis that FAST-FES training, which incorporates task-specific sensorimotor stimulation to paretic ankle muscles, would induce greater upregulation of lesioned corticospinal tract (CST) excitability compared to dose-matched training without FES in individuals post-stroke. In this repeated-measures crossover study, 11 participants >6 months post-stroke (66.25 ± 8.15 years, six females) received FAST-FES or FAST gait training protocols (comprising three training sessions) in a randomized order, with an intervening >3-week washout period. FES was applied to the paretic dorsi- and plantar-flexor muscles during the paretic swing and terminal stance phases of gait, respectively. CST excitability was measured before and after each training protocol from bilateral tibialis anterior and soleus muscles in three different test positions: sit-rest, sit-active, and quiet standing. We found a significant main effect of intervention on training-induced change in motor evoked potential (MEP) amplitude ( =0.02). Post hoc comparisons revealed that FAST-FES caused a larger training-induced increase in MEPs than FAST training ( =0.01). FAST-FES did not affect CST excitability of the nonlesioned hemisphere, with no significant changes in MEP amplitude of the nonparetic ankle muscles. FAST-FES training increased corticospinal excitability in paretic ankle muscles without upregulating nonparetic ankle corticospinal drive, suggesting preferential induction of neuroplasticity in the lesioned CST.

Background Paretic propulsion [measured as anteriorly-directed ground reaction forces (AGRF)] and trailing limb angle (TLA) show robust inter-relationships, and represent two key modifiable post-stroke gait variables that have biomechanical and clinical relevance. Our recent work demonstrated that real-time biofeedback is a feasible paradigm for modulating AGRF and TLA in able-bodied participants. However, the effects of TLA biofeedback on gait biomechanics of post-stroke individuals are poorly understood. Thus, our objective was to investigate the effects of unilateral, real-time, audiovisual TLA versus AGRF biofeedback on gait biomechanics in post-stroke individuals. Methods Nine post-stroke individuals (6 males, age 63 ± 9.8 years, 44.9 months post-stroke) participated in a single session of gait analysis comprised of three types of walking trials: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback unilaterally targeted deficits on the paretic limb. Dependent variables included peak AGRF, TLA, and ankle plantarflexor moment. One-way repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons were conducted to detect the effect of biofeedback on gait biomechanics variables. Results Compared to no-biofeedback, both AGRF and TLA biofeedback induced unilateral increases in paretic AGRF. TLA biofeedback induced significantly larger increases in paretic TLA than AGRF biofeedback. AGRF biofeedback increased ankle moment, and both feedback conditions increased non-paretic step length. Both types of biofeedback specifically targeted the paretic limb without inducing changes in the non-paretic limb. Conclusions By showing comparable increases in paretic limb gait biomechanics in response to both TLA and AGRF biofeedback, our novel findings provide the rationale and feasibility of paretic TLA as a gait biofeedback target for post-stroke individuals. Additionally, our results provide preliminary insights into divergent biomechanical mechanisms underlying improvements in post-stroke gait induced by these two biofeedback targets. We lay the groundwork for future investigations incorporating greater dosages and longer-term therapeutic effects of TLA biofeedback as a stroke gait rehabilitation strategy. Trial registration NCT03466372