p-IgGen: a paired antibody generative language model.

Summary: A key challenge in antibody drug discovery is designing novel sequences that are free from developability issues-such as aggregation, polyspecificity, poor expression, or low solubility. Here, we present p-IgGen, a protein language model for paired heavy-light chain antibody generation. The model generates diverse, antibody-like sequences with pairing properties found in natural antibodies.

A comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs.

Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics.

The Observed T Cell Receptor Space database enables paired-chain repertoire mining, coherence analysis, and language modeling.

T cell activation is governed through T cell receptors (TCRs), heterodimers of two sequence-variable chains (often an α and β chain) that synergistically recognize antigen fragments presented on cell surfaces. Despite this, there only exist repositories dedicated to collecting single-chain, not paired-chain, TCR sequence data. We addressed this gap by creating the Observed TCR Space (OTS) database, a source of consistently processed and annotated, full-length, paired-chain TCR sequences.

Separated at birth: Rediscovering the lost emotions in Luria's Working Brain.

Aleksandr Luria repeatedly emphasised the importance of emotions and the right hemisphere in his neuropsychological writings. It is surprising, therefore, that Luria's most influential book, The Working Brain, appears to lack an explicit section on these topics. This is especially notable because of a comment in the book's English-language Introduction, by Karl Pribram, referencing Luria's thoughts about precisely this material.

"We can all relate": patient experience of an emotion-oriented group intervention after Acquired Brain Injury.

Introduction: Group interventions are carried out routinely across neuropsychological rehabilitation services, to improve understanding of brain injury and aspects of impairment. Treatment provided in a group modality can bring additional perceived benefits, such as co-operative learning. However, there are very few studies which explore patient perceptions and experiences of such interventions.

Contextualising the developability risk of antibodies with lambda light chains using enhanced therapeutic antibody profiling.

Antibodies with lambda light chains (λ-antibodies) are generally considered to be less developable than those with kappa light chains (κ-antibodies). Though this hypothesis has not been formally established, it has led to substantial systematic biases in drug discovery pipelines and thus contributed to kappa dominance amongst clinical-stage therapeutics. However, the identification of increasing numbers of epitopes preferentially engaged by λ-antibodies shows there is a functional cost to neglecting to consider them as potential lead candidates.

"Talk and Chalk": An emotion regulation intervention for anger after acquired brain injury.

Uncontrollable anger is a debilitating consequence of acquired brain injury (ABI). This proof-of-concept study investigated the preliminary efficacy of an emotion regulation intervention for managing post-ABI anger. A secondary objective was to determine which participant characteristics were related to intervention gains.

A Small Step Toward Generalizability: Training a Machine Learning Scoring Function for Structure-Based Virtual Screening.

Over the past few years, many machine learning-based scoring functions for predicting the binding of small molecules to proteins have been developed. Their objective is to approximate the distribution which takes two molecules as input and outputs the energy of their interaction. Only a scoring function that accounts for the interatomic interactions involved in binding can accurately predict binding affinity on unseen molecules.

The Bangor Gambling Task: Computerized replication and reappraisal of an emotion-based decision task.

Emotion-based decision making (EBDM) is the capacity to make decisions based on prior emotional consequences of actions. Several neuropsychological tasks, using different gambling paradigms and with different levels of complexity, have been designed to assess EBDM. The Bangor Gambling Task (BGT) was created as a brief and simple card gambling-task to assess EBDM.

Like a rolling stone: Psychotherapy without (episodic) memory.

People with profound amnesia still retain the capacity to learn about the value of experiences, which is crucial in developing and sustaining interpersonal relationships. In a 2017 paper, we demonstrated for the first time (with patient JL) that transferential feelings develop the therapeutic process, despite profound episodic memory impairment after medial temporal lesions. This paper reports a second case (GA) of a profoundly amnesic patient in psychotherapy, this time after lesions to the anterior fornix.

Shades of Rage: Applying the Process Model of Emotion Regulation to Managing Anger After Brain Injury.

Uncontrollable anger is common following an acquired brain injury (ABI), with impaired emotion regulation (ER) being one of the main contributors. Existing psychological interventions appear moderately effective, though studies typically include limitations such as small sample sizes, issues of long-term efficacy, and standardization of content. While ER has been a popular research field, the study of ER for anger management after ABI is less well investigated, and contains few interventions based on the widely used Process Model of ER.

Post-Traumatic Growth in Professionals Caring for People with Intellectual Disabilities during COVID-19: A Psychological Intervention.

Background: Health professionals present a greater vulnerability to the effects of COVID-19 on their mental health, especially those who work with vulnerable groups such as those who suffer from intellectual disability (ID). The objective of the present research was to develop and verify the effectiveness of a psychological intervention for professionals in the field of ID to improve their mental health during this health crisis.

Methods: A total of 32 professionals participated.

Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

Objective: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment.

Design: Explorative, nonrandomized, clinical trial.

Setting: Patients receiving ambulatory care and control participants from the general community.

The Neuropsychology of Emotion and Emotion Regulation: The Role of Laterality and Hierarchy.

Over the last few decades, work in affective neuroscience has increasingly investigated the neural basis of emotion. A central debate in the field, when studying individuals with brain damage, has been whether emotional processes are lateralized or not. This review aims to expand this debate, by considering the need to include a dimension to the problem.

This time it's personal: reappraisal after acquired brain injury.

Reappraisal is a widely investigated emotion regulation strategy, often impaired in those with acquired brain injury (ABI). Little is known, however, about the tools to measure this capacity in patients, who may find traditional reappraisal tasks difficult. Fifty-five participants with ABI, and thirty-five healthy controls (HCs), completed reappraisal tasks with personal and impersonal emotion elicitation components, questionnaires measuring reappraisal (the ERQ-CA), and neuropsychological assessment.

The Erogenous Mirror: Intersubjective and Multisensory Maps of Sexual Arousal in Men and Women.

Erogenous zones of the body are sexually arousing when touched. Previous investigations of erogenous zones were restricted to the effects of touch on one's own body. However, sexual interactions do not just involve being touched, but also involve touching a partner and mutually looking at each other's bodies.

Building the bond: Predictors of the alliance in neurorehabilitation.

Background: Neurorehabilitation services are often delivered through group psycho-education programmes. However, little is known about the therapeutic process at work during such sessions. The present study is the first to gain insight into the therapeutic alliance, during a seven-session group programme.

Good things better? Reappraisal and discrete emotions in acquired brain injury.

There has been substantial interest in emotion after acquired brain injury (ABI), but less attention paid to emotion (ER). Research has focused primarily on the ER strategy of reappraisal for regulating negative emotions, without distinguishing between classes of emotion, and there has been no attempt at exploring these differences in patients with ABI. The present study explored components of reappraisal, across classes of emotion, and their associated neuropsychological mechanisms.

Preserved re-experience of discrete emotions: Amnesia and executive function.

Amnesic patients can re-experience emotions elicited by forgotten events, suggesting that brain systems for episodic and emotional memory are independent. However, the range of such emotional memories remains under-investigated (most studies employing just positive-negative emotion dyads), and executive function may also play a role in the re-experience of emotions. This is the first investigation of the intensity of the emotional re-experience of a range of discrete emotions (anger, fear, sadness, and happiness) for a group of amnesic patients.

Observations on Working Psychoanalytically with a Profoundly Amnesic Patient.

Individuals with profound amnesia are markedly impaired in explicitly recalling new events, but appear to preserve the capacity to use information from other sources. Amongst these preserved capacities is the ability to form new memories of an nature - a skill at the heart of developing and sustaining interpersonal relationships. The psychoanalytic study of individuals with profound amnesia might contribute to the understanding the importance of each memory system, including effects on key analytic processes such as transference and countertransference.

Alcohol exposure during pregnancy altered childhood developmental trajectories in a rural South African community.

Aim: This study examined the effects of prenatal alcohol exposure on childhood development trajectories in a rural South African community between 2003 and 2008.

Methods: We assessed 121 children at 7-12 months (year one) and 5-6 years (year five) using the Griffiths Mental Developmental Scales - Extended Revised, which measures sensorimotor, cognitive and social development, with lower scores indicating developmental delay. We also interviewed their mothers or caregivers.

Computational EEG modelling of decision making under ambiguity reveals spatio-temporal dynamics of outcome evaluation.

Complex human cognition, such as decision-making under ambiguity, is reflected in dynamic spatio-temporal activity in the brain. Here, we combined event-related potentials with computational modelling of the time course of decision-making and outcome evaluation during the Iowa Gambling Task. Measures of choice probability generated using the Prospect Valence Learning Delta (PVL-Delta) model, in addition to objective trial outcomes (outcome magnitude and valence), were applied as regressors in a general linear model of the EEG signal.

Confabulation: Developing the 'emotion dysregulation' hypothesis.

Confabulations offer unique opportunities for establishing the neurobiological basis of delusional thinking. As regards causal factors, a review of the confabulation literature suggests that neither amnesia nor executive impairment can be the sole (or perhaps even the primary) cause of all delusional beliefs - though they may act in concert with other factors. A key perspective in the modern literature is that many delusions have an emotionally positive or 'wishful' element, that may serve to modulate or manage emotional experience.