Plus, pretend you're moderating a forum like it's 2007 again. Welcome to our latest roundup of what's going on in the indie game space. As ever, we've got some neat new games for you to dive into this weekend, as well as a peek at some of the goodies headed our way in the near future. In between playing and trying to figure out whether the Steam Machine that's now under my TV actually fits into my life at all, I've been dipping into a -inspired project. is a simulation game that tasks you with moderating a forum in the mid-2000s, with a Windows XP-style UI adeptly setting the scene. There's even a desktop music player called Winump and a screensaver that kicks in after a period of inactivity. You'll have to review users' posts to determine whether they comply with a set of ever-changing rules, all while dealing with distractions like pop-ups and NSM Messenger pings.

Plus, the Steam Summer Sale is under way. Welcome to our latest roundup of what's going on in the indie game space. If you're looking for something new to play this weekend, we have several options for you to check out. We've also got news to bring you about upcoming games, including one with sword-wielding dinosaurs. Despite already having more games in my various libraries than I can ever conceivably play, I'm sure I'll at least pick up a few things from my wishlist.

The function of biomolecules such as proteins depends on their ability to interconvert between a wide range of structures or "conformations." Researchers have endeavored for decades to develop computational methods to predict the distribution of conformations, which is far harder to determine experimentally than a static folded structure. We present ConforMix, an inference-time algorithm that enhances sampling of conformational distributions using a combination of classifier guidance, filtering, and free energy estimation. Our approach upgrades diffusion models--whether trained for static structure prediction or conformational generation--to enable more efficient discovery of conformational variability without requiring prior knowledge of major degrees of freedom. ConforMix is orthogonal to improvements in model pretraining and would benefit even a hypothetical model that perfectly reproduced the Boltzmann distribution. Remarkably, when applied to a diffusion model trained for static structure prediction, ConforMix captures structural changes including domain motion, cryptic pocket flexibility, and transporter cycling, while avoiding unphysical states. Case studies of biologically critical proteins demonstrate the scalability, accuracy, and utility of this method.

In single-cell perturbation prediction, a central task is to forecast the effects of perturbing a gene unseen in the training data. The efficacy of such predictions depends on two factors: (1) the similarity of the target gene to those covered in the training data, which informs model (epistemic) uncertainty, and (2) the quality of the corresponding training data, which reflects data (aleatoric) uncertainty. Both factors are critical for determining the reliability of a prediction, particularly as gene perturbation is an inherently stochastic biochemical process. In this paper, we propose PRESCRIBE (PREdicting Single-Cell Response wIth Bayesian Estimation), a multivariate deep evidential regression framework designed to measure both sources of uncertainty jointly. Our analysis demonstrates that PRESCRIBE effectively estimates a confidence score for each prediction, which strongly correlates with its empirical accuracy. This capability enables the filtering of untrustworthy results, and in our experiments, it achieves steady accuracy improvements of over 3% compared to comparable baselines.

Virtual screening (VS) is a critical component of modern drug discovery, yet most existing methods--whether physics-based or deep learning-based--are developed around holo protein structures with known ligand-bound pockets. Consequently, their performance degrades significantly on apo or predicted structures such as those from AlphaFold2, which are more representative of real-world early-stage drug discovery, where pocket information is often missing. In this paper, we introduce an alignment-and-aggregation framework to enable accurate virtual screening under structural uncertainty. Our method comprises two core components: (1) a tri-modal contrastive learning module that aligns representations of the ligand, the holo pocket, and cavities detected from structures, thereby enhancing robustness to pocket localization error; and (2) a cross-attention based adapter for dynamically aggregating candidate binding sites, enabling the model to learn from activity data even without precise pocket annotations. We evaluated our method on a newly curated benchmark of apo structures, where it significantly outperforms state-of-the-art methods in blind apo setting, improving the early enrichment factor (EF1%) from 11.75 to 37.19. Notably, it also maintains strong performance on holo structures. These results demonstrate the promise of our approach in advancing firstin-class drug discovery, particularly in scenarios lacking experimentally resolved protein-ligand complexes. Our implementation is publicly available at https: //github.com/Wiley-Z/AANet.

Real-time decoding of target variables from multiple simultaneously recorded neural time-series modalities, such as discrete spiking activity and continuous field potentials, is important across various neuroscience applications. However, a major challenge for doing so is that different neural modalities can have different timescales (i.e., sampling rates) and different probabilistic distributions, or can even be missing at some time-steps. Existing nonlinear models of multimodal neural activity do not address different timescales or missing samples across modalities. Further, some of these models do not allow for real-time decoding. Here, we develop a learning framework that can enable real-time recursive decoding while nonlinearly aggregating information across multiple modalities with different timescales and distributions and with missing samples. This framework consists of 1) a multiscale encoder that nonlinearly aggregates information after learning within-modality dynamics to handle different timescales and missing samples in real time, 2) a multiscale dynamical backbone that extracts multimodal temporal dynamics and enables real-time recursive decoding, and 3) modality-specific decoders to account for different probabilistic distributions across modalities. In both simulations and three distinct multiscale brain datasets, we show that our model can aggregate information across modalities with different timescales and distributions and missing samples to improve real-time target decoding. Further, our method outperforms various linear and nonlinear multimodal benchmarks in doing so.

This is a month to look out for some powerful new books, with authors taking on challenges of all sorts and imagining whole new worlds. There are fresh ways to think about a cancer diagnosis, a book tackling the real inner world of hormones, in which we are all hormonal all the time, plus a major re-envisioning of the natural world where we abandon the shallows of competition for the depth and intricacies of connection and togetherness. It's quite hard going to get an up-to-date grip on human evolution, even for the best-briefed adult, so a book with sophisticated text and excellent illustrations and diagrams can only be a good thing. Especially if it is curated and edited by Alice Roberts, biological anthropologist, palaeopathologist, broadcaster - and professor of public engagement in science at the University of Birmingham, UK. She worked with a generous-sized international team of experts in many fields of human evolution, including archaeology, palaeontology, anthropology and cognitive science.

A majority stake of the indie game publisher Playstack is being sold to an investment company called Integrated Media Company (IMG). As first reported by Game Developer, the owner of the publisher behind hits like Balatro and is selling an 84.5 percent stake to a subsidiary of IMG called VantageCo Limited for £112.4 million, or around $151 million. Playstack also released a brief and vague statement from its founder and CEO, Harvey Elliott, that said this step represented a change in ownership, rather than a change in who we are. IMG's portfolio didn't previously include video game publishers but the company also owns the Fandom umbrella of brands, which includes Fandom, GameSpot, metacritic and more. It's hard to say what this acquisition means for the deck-building roguelite that won the hearts of the Engadget squad after its release in 2024.