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\"Experience all of Neal Adams' legendary Batman work--covers and stories--in chronological order! Batman by Neal Adams Book One contains Adams' contributions to the Dark Knight's legacy from 1967 through 1969, showing the process of introduction, adaption and innovation that the young artist brought to this legendary crime-fighter! Over the years, only a handful of artists have truly shaped the look of DC Comics' Batman. But since the original creation of the character in the 1930s by Bob Kane and Bill Finger, undoubtedly the most influential individual to take up the mantle of the Bat is Neal Adams. Beginning in the late 1960s and continuing through the 1970s, Adams' reimagining of \"the Batman\" revitalized the Caped Crusader for an entire generation of fans, rescuing him from TV-inspired campiness and returning him to his roots as a shadowy urban vigilante. In Adams' talented hands, Batman matured into \"the Dark Knight\"--a transformation that not only delighted readers and inspired his creative peers, but also planted the seeds for the 21st century's explosive growth of comics and superheroes into every corner of the world's popular culture.\"-- Provided by publisher.

Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies 1 , 2 ; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients with hepatocellular carcinoma 3 . The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis) 4 , 5 . Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53 . A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. Sertraline suppressed mTOR signalling, and selective drugs that target this pathway were highly effective in causing the apoptotic cell death of hepatocellular carcinoma cells treated with a CDC7 inhibitor. The feedback reactivation of mTOR signalling after its inhibition 6 is blocked in cells that have been treated with a CDC7 inhibitor, which leads to the sustained inhibition of mTOR and cell death. Using multiple in vivo mouse models of liver cancer, we show that treatment with combined inhibition of of CDC7 and mTOR results in a marked reduction of tumour growth. Our data indicate that exploiting an induced vulnerability could be an effective treatment for liver cancer. CDC7 inhibition selectively induces senescence in hepatocellular carcinoma cells with TP53 mutations, which enables the selective apoptotic cell death of these senescent cells using inhibitors of mTOR signalling.

Mindfulness practice has been proposed as enabling an individual to purposefully increase attention enabling the individual to be more present in the moment, open-minded and accepting. As such mindfulness practice may offer an important mechanism to promote positive psychological health and wellbeing through changes to the stress appraisal process. The aim of this study was to investigate the impact of a simple mindfulness drawing task on dimensions of psychology instrumental in appraisal and health. 65 participants were allocated to one of two conditions (Shambala colouring, Control). The mindfulness group was found to report significantly higher levels of observational ability and non-judgement (p < 0.05) amongst several other differences. This work focused upon the claim of effectiveness of a brief mindfulness task to modify mindfulness focused psychological variables.

The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR activation might also have anti-proliferative action on tumours, the underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the mechanisms of glucocorticoid response, focusing on lung cancer. We show that GR activation induces reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. GR-induced dormancy is dependent on a single GR-target gene, CDKN1C , regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anticancer therapy related side-effects. Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.

Given an infinite connected regular graph G = (V ,E), place at each vertex Poisson(λ) walkers performing independent lazy simple random walks on G simultaneously. When two walkers visit the same vertex at the same time they are declared to be acquainted. We show that when G is vertex-transitive and amenable, for all λ > 0 a.s. any pair of walkers will eventually have a path of acquaintances between them. In contrast, we show that when G is nonamenable (not necessarily transitive) there is always a phase transition at some λ c(G) > 0. We give general bounds on λ c(G) and study the case that G is the d-regular tree in more detail. Finally, we show that in the nonamenable setup, for every λ there exists a finite time tλ(G) such that a.s. there exists an infinite set of walkers having a path of acquaintances between them by time tλ(G).

DNA double-strand breaks are repaired by multiple pathways, including non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ). The balance of these pathways is dependent on the local chromatin context, but the underlying mechanisms are poorly understood. By combining knockout screening with a dual MMEJ:NHEJ reporter inserted in 19 different chromatin environments, we identified dozens of DNA repair proteins that modulate pathway balance dependent on the local chromatin state. Proteins that favor NHEJ mostly synergize with euchromatin, while proteins that favor MMEJ generally synergize with distinct types of heterochromatin. Examples of the former are BRCA2 and POLL, and of the latter the FANC complex and ATM. Moreover, in a diversity of human cancer types, loss of several of these proteins alters the distribution of pathway-specific mutations between heterochromatin and euchromatin. Together, these results uncover a complex network of proteins that regulate MMEJ:NHEJ balance in a chromatin context-dependent manner. DNA double-strand breaks are repaired by multiple pathways. The balance of these pathways depends on the local chromatin context, but the underlying mechanisms are poorly understood. Here the authors uncover a network of proteins that regulate pathway balance in a chromatin context-dependent manner.

Background DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. In mammalian cells, DDT is regulated by two independent pathways, controlled by the polymerase REV1 and ubiquitinated PCNA, respectively. Results To determine the molecular and genomic impact of a global DDT defect, we studied Pcna K164R/− ;Rev1 −/− compound mutants in mouse cells. Double-mutant cells display increased replication stress, hypersensitivity to genotoxic agents, replication speed, and repriming. A whole-genome CRISPR-Cas9 screen revealed a strict reliance of double-mutant cells on the CST complex, where CST promotes fork stability. Whole-genome sequencing indicated that this double-mutant DDT defect favors the generation of large, replication-stress inducible deletions of 0.4–4.0 kbp, defined as type 3 deletions. Junction break sites of these deletions reveal microhomology preferences of 1–2 base pairs, differing from the smaller type 1 and type 2 deletions. These differential characteristics suggest the existence of molecularly distinct deletion pathways. Type 3 deletions are abundant in human tumors, can dominate the deletion landscape, and are associated with DNA damage response status and treatment modality. Conclusions Our data highlight the essential contribution of the DDT system to genome maintenance and type 3 deletions as mutational signature of replication stress. The unique characteristics of type 3 deletions implicate the existence of a novel deletion pathway in mice and humans that is counteracted by DDT. Graphical Abstract

IntroductionThe HOPSCOTCH study ‘Helping Optimise Primary Care Support During Transition From Children’s Hospice Care’ aims to develop a toolbox to enable engagement of primary care services in the care of young people with life-limiting conditions (LLC) with a specific focus on the point of transition from children’s hospice services.Methods and analysisIndividual interviews will be held with young people with LLC, their families and healthcare professionals (HCPs). In alignment with Experience Based Co-Design (EBCD) methodology, extracts of film and audio from young people and family interviews will be combined to professionally produce a ‘catalyst film’ highlighting key points and experiences before, during and after the transition from children’s hospice care. Role-specific workshops will be held with young people with LLC, their families and HCPs working in primary care, children’s hospices and adult hospice services. The catalyst film will be used in feedback workshops to prompt prioritisation of key issues to take forward into toolbox development in a shared young people, family and HCP workshop. A documentary analysis of resources currently used to support transition and communication between care settings will support contextual understanding of the transition process. Young people, parents and professionals have shaped and continue to have influence over the study delivery as advisors alongside a multidisciplinary steering committee.The study design has been guided by the UK Medical Research Council complex intervention framework. Intervention development draws on the principles of EBCD and is theoretically driven by the Behaviour Change Wheel.Ethics and disseminationThe study is registered with the UK’s Clinical Study Registry (ISCTRN75964234).Ethical approval was obtained from Wales 3 ethics board on 2 July 2025 (IRAS ID 334486). This study will include ongoing dissemination and knowledge transfer to key audiences (young people, parents, service providers, commissioners) via publications, national bodies, knowledge exchange events, web-based platforms, social media and clinical/academic forums.

Many young adults demonstrate insufficient rates of physical activity (PA) to yield health benefits. The study tested the effectiveness of a text messaging intervention targeting key psychological determinants and PA. Participants received either attitude messages, goal priority messages, a combination of these, or generic PA information (control). After confirming that groups were matched at baseline, a 2 (attitude: yes vs. no) by 2 (goal priority: yes vs. no) by 2 (time: immediately post-intervention, four weeks post-intervention) randomized control trial tested main and interactive effects. Results showed participants that received attitude messages had significantly more positive attitudes, intentions and rates of PA. Mediational analyses showed the influence of attitude messages on PA to be fully mediated through the serial path via attitude and intention. There were no other main or interactive effects. The study provides support for using attitudinal messages delivered via text messaging to influence key psychological determinants and PA.