Neurocognitive concerns and neurocognitive impairment in long-term survivors of oropharyngeal cancer post (chemo)radiotherapy.

Background: Little is known about neurocognitive concerns (NCC) and neurocognitive function (NCF) in survivors of oropharyngeal cancer (OPC) following (chemo)radiotherapy.

Methods: A multicentre cross-sectional study was conducted in non-surgically treated OPC. Using the Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog), NCC were classed as having concerns at least some of the time (MOS-Cog score of ≤ 60 across all items).

C[double bond, length as m-dash]O methylenation mediated by organo-alkali metal reagents: metal identity and ligand effects.

C[double bond, length as m-dash]O methylenation mediated by α-silyl organo-alkali metal reagents, namely Peterson methylenation, is a textbook organic reaction that has been widely employed in synthetic chemistry for over 50 years. The process is performed over two steps, by isolating the β-silyl alcohol intermediate generated nucleophilic addition and then subjecting it to elimination. The choices of alkali metal and external Lewis base ligand play a critical role in the elimination step, but the reasons remain poorly understood.

Cone-beam computed tomography reconstruction for a commercial proton beam therapy system.

Background & Purpose: Cone-beam computed tomography (CBCT) images are used in image-guided radiotherapy to track anatomical changes throughout treatment and to set up patients to ensure accurate delivery of therapeutic radiation at each treatment session. An offline method of CBCT reconstruction workflow, operating on 2D projection images and specific to the imaging system in question, is needed for many image optimisation studies. Here we present a methodology to reconstruct CBCT images from these data for a commercial proton beam therapy machine, accounting for the variation in exposure and beam hardening from filtration due to gantry rotation during CBCT acquisition.

APPROACH: Analysis of Proton versus Photon Radiotherapy in Oligodendroglioma and Assessment of Cognitive Health - study protocol paper for a phase III multicentre, open-label randomised controlled trial.

Introduction: Oligodendroglioma (ODG) is a rare type of brain tumour, typically diagnosed in younger adults and associated with prolonged survival following treatment. The current standard of care is maximal safe debulking surgery, radiotherapy (RT) and adjuvant procarbazine, lomustine and vincristine (PCV) chemotherapy. Patients may experience long-term treatment-related toxicities, with RT linked to impairments of neurocognitive function (NCF) and health-related quality of life (HRQoL).

Shame, Guilt and Psychedelic Experience: Results from a Prospective, Longitudinal Survey of Real-World Psilocybin Use.

The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. Despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of shame-related processes with psychedelic use. This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use.

Multidimensional fatigue and its impact on work productivity, mood and quality of life in long-term survivors following definitive intensity-modulated radiotherapy for oropharyngeal cancer: A cross-sectional study.

Purpose: Radiotherapy (RT) for oropharyngeal cancer (OPC) can lead to late toxicity. Fatigue is a known debilitating issue for many cancer survivors, yet prevalence and severity of long-term fatigue in patients treated for OPC is unknown.

Method: As part of a mixed-methods study, fatigue in OPC patients ≥ 2 years post RT + / - chemotherapy was evaluated.

Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study.

Recent studies suggest psychedelic use may be associated with changes in a variety of beliefs or belief-like states, including increased 1) mind perception, 2) non-naturalistic beliefs, and 3) Atheist-Believer status (e.g. believer, agnostic, or nonbeliever).

An observational time-series study on the behavioral effects of adjunctive artisanal cannabidiol use by adults with treatment resistant epilepsies.

Background: For approximately 30% of people with epilepsy, seizures are not well-controlled by anti-seizure medication (ASM). This condition, called treatment resistant epilepsy (TRE), is associated with increased morbidity and mortality, and substantially impacts the quality of life of both the individual and their family. Non-responsiveness to ASMs leads many people with TRE to seek alternative therapies, such as cannabinoid-based medication, particularly cannabidiol (CBD), with or without medical or professional advice.

Long-term benefits to psychological health and well-being after ceremonial use of Ayahuasca in Middle Eastern and North African immigrants and refugees.

Background: Refugees and immigrants can experience complex stressors from the process of immigration that can have lasting and severe long-term mental health consequences. Experiences after ayahuasca ingestion are shown to produce positive effects on psychological wellbeing and mental health, including anecdotal reports of improved symptoms of trauma and related disorders. However, data on the longitudinal health impact of naturalistic ayahuasca use in Middle Eastern and North African (MENA) immigrant and refugee populations is limited.

"Why am I still suffering?": Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy.

Background: Late effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck-specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives.

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode.

Background: The first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect.

Reconstituted ovaries self-assemble without an ovarian surface epithelium.

Three-dimensional (3D) stem cell models of the ovary have the potential to benefit women's reproductive health research. One such model, the reconstituted ovary (rOvary) self-assembles with pluripotent stem cell-derived germ cells creating a 3D ovarian mimic competent to support the differentiation of functional oocytes inside follicles. In this study, we evaluated the cellular composition of the rOvary revealing the capacity to generate multiple follicles surrounded by NR2F2+ stroma cells.

Naturalistic psilocybin use is associated with persisting improvements in mental health and wellbeing: results from a prospective, longitudinal survey.

Introduction: The classic psychedelic psilocybin, found in some mushroom species, has received renewed interest in clinical research, showing potential mental health benefits in preliminary trials. Naturalistic use of psilocybin outside of research settings has increased in recent years, though data on the public health impact of such use remain limited.

Methods: This prospective, longitudinal study comprised six sequential automated web-based surveys that collected data from adults planning to take psilocybin outside clinical research: at time of consent, 2 weeks before, the day before, 1-3 days after, 2-4 weeks after, and 2-3 months after psilocybin use.

Neurocognitive function following (chemo)radiotherapy for nasopharyngeal cancer and other head and neck cancers: A systematic review.

When radiotherapy is used in the treatment of head and neck cancers, the brain commonly receives incidental doses of radiotherapy with potential for neurocognitive changes and subsequent impact on quality of life. This has not been widely investigated to date. A systematic search of MEDLINE, EMBASE, Psycinfo Info and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases was conducted.

TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.

Treatment planning considerations for the development of FLASH proton therapy.

With increasing focus on the translation of the observed FLASH effect into clinical practice, this paper presents treatment planning considerations for its development using proton therapy. Potential requirements to induce a FLASH effect are discussed along with the properties of existing proton therapy delivery systems and the changes in planning and delivery approaches required to satisfy these prerequisites. For the exploration of treatment planning approaches for FLASH, developments in treatment planning systems are needed.

Cochlea to categories: The spatiotemporal dynamics of semantic auditory representations.

How does the auditory system categorize natural sounds? Here we apply multimodal neuroimaging to illustrate the progression from acoustic to semantically dominated representations. Combining magnetoencephalographic (MEG) and functional magnetic resonance imaging (fMRI) scans of observers listening to naturalistic sounds, we found superior temporal responses beginning ∼55 ms post-stimulus onset, spreading to extratemporal cortices by ∼100 ms. Early regions were distinguished less by onset/peak latency than by functional properties and overall temporal response profiles.

EED is required for mouse primordial germ cell differentiation in the embryonic gonad.

Development of primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs, which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created an EED conditional knockout mouse and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes.

Improving workflow for adaptive proton therapy with predictive anatomical modelling: A proof of concept.

Purpose: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer.

Methods: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model.

Estimating the percentage of patients who might benefit from proton beam therapy instead of X-ray radiotherapy.

Objectives: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision.

Intra-Rater and Inter-Rater Reliability of Pressure Pain Algometry of the Sural and Tibial Nerves in Asymptomatic Elite Youth Footballers.

Ankle injuries are highly prevalent in elite youth footballers and increase the mechanosensitivity of the local neural tissue, which may predispose athletes to re-injury and prolong rehabilitation periods. Increased neural mechanosensitivity presents clinically as altered pain pressure thresholds (PPTs) which are measured with pressure algometry. The purpose of this study was to determine the intra-rater and inter-rater reliability of PPTs of the ankle neural tissue in asymptomatic elite youth football players.