Acceptability of Tele-mental Health Services Among Users: A Systematic Review and Meta-analysis.

BACKGROUND: Mental disorders are currently a global public health concern, particularly after the coronavirus disease 2019 (COVID-19) pandemic. Mental health services gradually transitioned to teleservices, employing various methods like texting and videoconferencing. This meta-analysis aimed mainly to quantify the acceptability of tele-mental health services among both beneficiaries and providers. Secondary objectives included quantifying the usability of and satisfaction with these services. METHODS: We conducted a systematic search of the following databases PubMed Central, SAGE, Google Scholar, Scopus, Web of Science, PubMed Medline, and EBSCO according to Preferred Reporting Items of the Systematic Reviews and Meta-Analysis (PRISMA) guidelines until December 2022. RESULTS: Out of 3366 search results, 39 studies fully met the inclusion criteria. The pooled acceptability of tele-mental health services among beneficiaries was [71.0% with a 95% confidence interval (CI) of 63.0 - 78.5%, I2 = 98%]. Using meta-regression, four key factors contributed to this heterogeneity (R2 = 99.75%), namely, year of publication, type of mental disorder, participant category, and the quality of included studies. While acceptability among providers was [66.0% (95%CI, 52.0 - 78.0%), I2 = 95%]. The pooled usability of tele-mental health services among participants was [66.0% (95%CI, 50.0 - 80.0%), I2 = 83%]. Subgroup analysis revealed statistically significant results (p = 0.003), indicating that usability was higher among beneficiaries compared to providers. CONCLUSIONS: The study highlighted a high acceptability of tele-mental health services. These findings suggest a promising outlook for the integration and adoption of tele-mental health services and emphasize the importance of considering user perspectives and addressing provider-specific challenges to enhance overall service delivery and effectiveness.

Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease.

The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson's disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. Whilst acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD.

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.

Accessing the human trophoblast stem cell state from pluripotent and somatic cells.

Trophoblasts are specialized epithelial cells that perform critical functions during blastocyst implantation and mediate maternal-fetal communication during pregnancy. However, our understanding of human trophoblast biology remains limited since access to first-trimester placental tissue is scarce, especially between the first and fourth weeks of development. Moreover, animal models inadequately recapitulate unique aspects of human placental physiology. In the mouse system, the isolation of self-renewing trophoblast stem cells has provided a valuable in vitro model system of placental development, but the derivation of analogous human trophoblast stem cells (hTSCs) has remained elusive until recently. Building on a landmark study reporting the isolation of bona fide hTSCs from blastocysts and first-trimester placental tissues in 2018, several groups have developed methods to derive hTSCs from pluripotent and somatic cell sources. Here we review the biological and molecular properties that define authentic hTSCs, the trophoblast potential of distinct pluripotent states, and methods for inducing hTSCs in somatic cells by direct reprogramming. The generation of hTSCs from pluripotent and somatic cells presents exciting opportunities to elucidate the molecular mechanisms of human placental development and the etiology of pregnancy-related diseases.

Malignant Peripheral Nerve Sheath Tumors of the Brachial Plexus: A Single-Center Experience on Diagnosis, Management, and Outcomes.

INTRODUCTION: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma. Malignant peripheral nerve sheath tumors are aggressive tumors with high rates of local recurrence and metastasis. The prognosis is poor with 5-year survival rates of 15% to 50%. Unfortunately, given the rarity of these tumors, it is not clear how to best manage these patients. The purposes of this study were (1) to discuss our experience with MPNST and particularly our difficulties with diagnosis and management, and (2) to review the literature. MATERIALS AND METHODS: We report on all tumors of the brachial plexus excised between 2013 and 2019. We report 3 cases of MPNST, their treatment, and their outcomes. RESULTS: Thirteen patients underwent surgical excision of an intrinsic brachial plexus mass. Three of these patients (2 male, 1 female; average age, 36 years) were diagnosed with an MPNST. Two patients with an MPNST had neurofibromatosis type 1. All patients with an MPNST had a tumor >8 cm, motor and sensory deficits, and pain. All 3 patients with MPNST underwent a magnetic resonance imaging (MRI) before diagnosis. The average time from initial symptom onset to MRI was 12.3 months. Only 1 of the MRIs suggested a malignant tumor, with no MRI identifying an MPNST. One patient underwent an excisional biopsy, and 2 had incisional biopsies. Because of the lack of diagnosis preoperatively, all patients had positive margins given the limited extent of surgery. Returning for excision in an attempt to achieve negative margins in a large oncologically contaminated field was not possible because defining the boundaries of the initial surgical field was unachievable; therefore, the initial surgery was their definitive surgical management. All patients were referred to oncology and received radiation therapy. CONCLUSIONS: Malignant peripheral nerve sheath tumors must be suspected in enlarging masses (>5 cm) with the constellation of pain, motor, and sensory deficits. Computed tomography- or ultrasound-guided core needle biopsy under brachial plexus block or sedation is required for definitive diagnosis to allow for a comprehensive approach to the patient's tumor with a higher likelihood of disease-free survival.

Reconstruction of Quadriceps Function Using a Single Functional Gracilis Muscle Transfer With an Adductor Longus Nerve to Femoral Nerve Branch of the Rectus Femoris Nerve Transfer.

BACKGROUND: A femoral nerve injury may result in cutaneous sensory disturbances of the anteromedial thigh and complete paralysis of the quadriceps femoris muscles resulting in an inability to extend the knee. The traditional mainstay of treatment for femoral neuropathy is early physiotherapy, knee support devices, and pain control. Case reports have used the anterior division of the obturator nerve as a donor nerve to innervate the quadriceps femoris muscles; however, a second nerve transfer or nerve grafting is often required for improved outcomes. We suggest a novel technique of combining an innervated, pedicled gracilis transfer with an adductor longus to rectus femoris nerve transfer to restore the strength and stability of the quadriceps muscles. METHODS: This is a case series describing the use of a pedicled gracilis muscle transposed into the rectus femoris position with a concomitant nerve transfer from the adductor longus nerve branch into the rectus femoris nerve branch to restore quadriceps function after iatrogenic injury (hip arthroplasty) and trauma (gunshot wound). RESULTS: With electrodiagnostic confirmation of severe denervation of the quadriceps muscles and no evidence of elicitable motor units, 2 patients (average age, 47 years) underwent a quadriceps muscle reconstruction with a pedicled, innervated gracilis muscle and an adductor longus to recuts femoris nerve transfer. At 1 year follow-up, the patients achieved 4.5/5 British Medical Research Council full knee extension, a stable knee, and the ability to ambulate without an assistive aid. CONCLUSIONS: The required amount of quadriceps strength necessary to maintain quality of life has not been accurately established. In the case of femoral neuropathy, we assumed that a nerve transfer alone and a gracilis muscle transfer alone would not provide enough stability and strength to restore quadriceps function. We believe that the restoration of the quadriceps function after femoral nerve injury can be achieved by combining an innervated, pedicled gracilis transfer with an adductor longus to rectus femoris nerve transfer with low morbidity and no donor defects.

What is underneath all that stuff? A Q-methodological exploration of profiles of beliefs and vulnerabilities in hoarding disorder.

BACKGROUND: Hoarding disorder (HD) can be understood through the cognitive behavioural model in the context of vulnerability factors (for example, personality traits, co-morbidities, traumatic life events) and beliefs about possessions (for example, identity, emotional attachment, memory, utility). Less is known about the strength of these hypothesised beliefs, or how they interact within the hoarding population, with researchers suggesting that specifying beliefs would improve treatment outcomes. AIM: The current study explored beliefs in HD, utilising Q-methodology to explore both categories of beliefs and the interactions between these. Moreover, Q-methodology allowed for comparison of the individuals endorsing specific categories of beliefs. METHOD: A comprehensive list of beliefs about possessions was developed. Thirty-two adults with clinically significant levels of HD completed a Q-sort task, alongside measures of proposed vulnerabilities, including co-morbidity, trauma and attachment style. RESULTS: Q-factor analysis produced four profiles consisting of groups of participants who endorsed the same beliefs and had shared characteristics: (1) 'Expression of identity', (2) 'Responsibility and morality', (3) 'Stability and predictability', and (4) 'Objects as emotional and meaningful beings'. DISCUSSION: The profiles were distinguished by different categories of beliefs and co-morbid symptoms, suggesting that more targeted assessment tools and interventions would be beneficial to account for this heterogeneity within the clinical population. In particular, beliefs about identity and self-concept formed the largest profile, and beliefs about stability and predictability introduce a novel category of beliefs.

Use of a human embryonic stem cell model to discover GABRP, WFDC2, VTCN1 and ACTC1 as markers of early first trimester human trophoblast.

Human placental development during early pregnancy is poorly understood. Many conceptuses are lost at this stage. It is thought that preeclampsia, intrauterine growth restriction and other placental syndromes that manifest later in pregnancy may originate early in placentation. Thus, there is a need for models of early human placental development. Treating human embryonic stem cells (hESCs) with BMP4 (bone morphogenic protein 4) plus A83-01 (ACTIVIN/NODAL signaling inhibitor) and PD173074 (fibroblast growth factor 2 or FGF2 signaling inhibitor) (BAP conditions) induces differentiation to the trophoblast lineage (hESCBAP), but it is not clear which stage of trophoblast differentiation these cells resemble. Here, comparison of the hESCBAP transcriptome to those of trophoblasts from human blastocysts, trophoblast stem cells and placentas collected in the first-third trimester of pregnancy by principal component analysis suggests that hESC after 8 days BAP treatment most resemble first trimester syncytiotrophoblasts. To further test this hypothesis, transcripts were identified that are expressed in hESCBAP but not in cultures of trophoblasts isolated from term placentas. Proteins encoded by four genes, GABRP (gamma-aminobutyric acid type A receptor subunit Pi), WFDC2 (WAP four-disulfide core domain 2), VTCN1 (V-set domain containing T-cell activation inhibitor 1) and ACTC1 (actin alpha cardiac muscle 1), immunolocalized to placentas at 4-9 weeks gestation, and their expression declined with gestational age (R2 = 0.61-0.83). None are present at term. Expression was largely localized to syncytiotrophoblast of both hESCBAP cells and placental material from early pregnancy. WFDC2, VTCN1 and ACTC1 have not previously been described in placenta. These results support the hypothesis that hESCBAP represent human trophoblast analogous to that of early first trimester and are a tool for discovery of factors important to this stage of placentation.

Clinical Consensus Guidelines on the Application of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease Diagnosis: Recommendations of the Irish Network for Biomarkers in Neurodegeneration.

It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-ß42 (Aß42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis. The outcome of this meeting was the formulation of a consensus statement paper for the benefit of health care professionals involved in the diagnosis and management of dementia to ensure appropriate use of these biomarker tests in clinical settings in Ireland.

Eph/ephrin interactions modulate muscle satellite cell motility and patterning.

During development and regeneration, directed migration of cells, including neural crest cells, endothelial cells, axonal growth cones and many types of adult stem cells, to specific areas distant from their origin is necessary for their function. We have recently shown that adult skeletal muscle stem cells (satellite cells), once activated by isolation or injury, are a highly motile population with the potential to respond to multiple guidance cues, based on their expression of classical guidance receptors. We show here that, in vivo, differentiated and regenerating myofibers dynamically express a subset of ephrin guidance ligands, as well as Eph receptors. This expression has previously only been examined in the context of muscle-nerve interactions; however, we propose that it might also play a role in satellite cell-mediated muscle repair. Therefore, we investigated whether Eph-ephrin signaling would produce changes in satellite cell directional motility. Using a classical ephrin 'stripe' assay, we found that satellite cells respond to a subset of ephrins with repulsive behavior in vitro; patterning of differentiating myotubes is also parallel to ephrin stripes. This behavior can be replicated in a heterologous in vivo system, the hindbrain of the developing quail, in which neural crest cells are directed in streams to the branchial arches and to the forelimb of the developing quail, where presumptive limb myoblasts emigrate from the somite. We hypothesize that guidance signaling might impact multiple steps in muscle regeneration, including escape from the niche, directed migration to sites of injury, cell-cell interactions among satellite cell progeny, and differentiation and patterning of regenerated muscle.

Strategies to prevent ventilation-associated pneumonia: the effect of cuff pressure monitoring techniques and tracheal tube type on aspiration of subglottic secretions: an in-vitro study.

BACKGROUND: Ventilation-associated pneumonia (VAP) is the commonest nosocomial infection in intensive care. Implementation of a VAP prevention care bundle is a proven method to reduce its incidence. The UK care bundle recommends maintenance of the tracheal tube cuff pressure at 20 to 30  cmH2O with 4-hourly pressure checks and use of tracheal tubes with subglottic aspiration ports in patients admitted for more than 72  h. OBJECTIVE: To evaluate the effects of tracheal tube type and cuff pressure monitoring technique on leakage of subglottic secretions past the tracheal tube cuff. DESIGN: Bench-top study. SETTING: Laboratory. INTERVENTIONS: A model adult trachea with simulated subglottic secretions was intubated with a tracheal tube with the cuff inflated to 25  cmH2O. Experiments were conducted using a Portex Profile Soft Seal tracheal tube with three cuff pressure monitoring strategies and using a Portex SACETT tracheal tube with intermittent cuff pressure checks. OUTCOME MEASURES: Rate of simulated secretion leakage past the tracheal tube cuff. RESULTS: Mean ±â€ŠSD leakage of fluid past the Profile Soft Seal tracheal tube cuff was 2.25 ±â€Š1.49  ml  min⁻¹ with no monitoring of cuff pressure, 2.98 ±â€Š1.63  ml  min⁻¹ with intermittent cuff pressure monitoring and 3.83 ±â€Š2.17  ml  min⁻¹ with continuous cuff pressure monitoring (P <0.001). Using a SACETT tracheal tube with a subglottic aspiration port and aspirating the simulated secretions prior to intermittent cuff pressure checks reduced the leakage rate to 0.50 ±â€Š0.48  ml  min⁻¹ (P <0.001). CONCLUSION: Subglottic secretions leaked past the tracheal tube cuff with all tube types and cuff pressure monitoring strategies in this model. Significantly higher rates were observed with continuous cuff pressure monitoring and significantly lower rates were observed when using a tracheal tube with a subglottic aspiration port. Further evaluation of medical device performance is needed in order to design more effective VAP prevention strategies.

Neuro-critical care: a valuable placement during foundation and early neurosurgical training.

INTRODUCTION: Neurosciences critical care units (NCCUs) present a unique opportunity to junior trainees in neurosurgery as well as foundation trainees looking to gain experience in the management of critically ill patients with neurological conditions. Placements in NCCUs are undertaken in the early years of neurosurgical training or during neurosciences themed foundation programmes. We sought to quantify the educational benefits of such placements from the trainee perspective. METHODS: Thirty-two trainees who had undertaken placements at Foundation Year 2 (FY2) to Specialty Trainee Year 3 (ST3) level between August 2009 and April 2013 were invited to take part in an online questionnaire survey. Competence in individual skills was self-rated on a ranked scale from one (never observed) to five (performed unsupervised) both before and after the placement. Trainees were also asked a series of questions pertaining to their ability to manage common neurosurgical conditions, as well as the perceived educational rigour of their placement. RESULTS: Twenty-three responses were received. Eighteen responses were from FY2s and seven were from ST1-3 level trainees. Following their placements, 100% of respondents felt better equipped to deal with neurosurgical and neurological emergencies and cranial trauma. Most felt better equipped to manage hydrocephalus (95.7%), polytrauma patients (95.7%), spontaneous intracranial haemorrhage (91.3%) and spinal trauma (82.6%). Significant increases were seen in experience in all practical skills assessed. These included central venous catheterisation (p < 0.001), intracranial pressure (ICP) bolt insertion (p < 0.001), ICP bolt removal (p < 0.001), external ventricular drain (EVD) insertion (p = 0.001) and tapping of EVD for cerebrospinal fluid sample (p < 0.001). CONCLUSION: Our results clearly demonstrate the educational benefits of NCCU placements in the early stages of a neurosurgical training programme as well as in the Foundation Programme. This supports the incorporation of a four- to six-month NCCU rotation in early years training as educationally valuable.

Generation of 3D Trophoblast Organoids from Human Naïve Pluripotent Stem Cells.

The human placenta is a transient organ that functions to support the needs of the fetus throughout gestation. Trophoblasts are the major epithelial cells found within the placenta and comprise a variety of distinct cell types with specialized roles in fetal-maternal communication. Our understanding of human trophoblast development remains limited due to ethical and legal restrictions on accessing first-trimester placental tissues, as well as the inability of common animal models to replicate primate placental development. It is therefore important to advance in vitro models of human trophoblast development as a basis for studying pregnancy-associated complications and diseases. In this chapter, we describe a protocol for generating 3D trophoblast organoids from naïve human pluripotent stem cells (hPSCs). The resulting stem-cell-derived trophoblast organoids (SC-TOs) contain distinct cytotrophoblast (CTB), syncytiotrophoblast (STB), and extravillous trophoblast (EVT) cell types, which closely correspond to trophoblast identities in the human post-implantation embryo. We discuss methods for characterizing SC-TOs by immunofluorescence, flow cytometry, mRNA and microRNA expression profiling, and placental hormone secretion. Furthermore, SC-TOs can undergo differentiation into specialized 3D EVT organoids, which display robust invasion when co-cultured with human endometrial cells. Thus, the protocol described herein offers an accessible 3D model system of human placental development and trophoblast invasion.

Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part II - Microscopic scales.

BACKGROUND: Although the benefits of breast screening and early diagnosis are known for reducing breast cancer mortality rates, the effects and risks of low radiation doses to the cells in the breast are still ongoing topics of study. PURPOSE: To study specific energy distributions ( f ( z , D g ) $f(z,D_{g})$ ) in cytoplasm and nuclei of cells corresponding to glandular tissue for different x-ray breast imaging modalities. METHODS: A cubic lattice (500 µm length side) containing 4064 spherical cells was irradiated with photons loaded from phase space files with varying glandular voxel doses ( D g $D_{g}$ ). Specific energy distributions were scored for nucleus and cytoplasm compartments using the PENELOPE (v. 2018) + penEasy (v. 2020) Monte Carlo (MC) code. The phase space files, generated in part I of this work, were obtained from MC simulations in a voxelized anthropomorphic phantom corresponding to glandular voxels for different breast imaging modalities, including digital mammography (DM), digital breast tomosynthesis (DBT), contrast enhanced digital mammography (CEDM) and breast CT (BCT). RESULTS: In general, the average specific energy in nuclei is higher than the respective glandular dose scored in the same region, by up to 10%. The specific energy distributions for nucleus and cytoplasm are directly related to the magnitude of the glandular dose in the voxel ( D g $D_{g}$ ), with little dependence on the spatial location. For similar D g $D_{g}$ values, f ( z , D g ) $f(z,D_{g})$ for nuclei is different between DM/DBT and CEDM/BCT, indicating that distinct x-ray spectra play significant roles in f ( z , D g ) $f(z,D_{g})$ . In addition, this behavior is also present when the specific energy distribution ( F g ( z ) $F_{g}(z)$ ) is considered taking into account the GDD in the breast. CONCLUSIONS: Microdosimetry studies are complementary to the traditional macroscopic breast dosimetry based on the mean glandular dose (MGD). For the same MGD, the specific energy distribution in glandular tissue varies between breast imaging modalities, indicating that this effect could be considered for studying the risks of exposing the breast to ionizing radiation.

Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part I - Macroscopic scales.

BACKGROUND: X-ray breast imaging modalities are commonly employed for breast cancer detection, from screening programs to diagnosis. Thus, dosimetry studies are important for quality control and risk estimation since ionizing radiation is used. PURPOSE: To perform multiscale dosimetry assessments for different breast imaging modalities and for a variety of breast sizes and compositions. The first part of our study is focused on macroscopic scales (down to millimeters). METHODS: Nine anthropomorphic breast phantoms with a voxel resolution of 0.5 mm were computationally generated using the BreastPhantom software, representing three breast sizes with three distinct values of volume glandular fraction (VGF) for each size. Four breast imaging modalities were studied: digital mammography (DM), contrast-enhanced digital mammography (CEDM), digital breast tomosynthesis (DBT) and dedicated breast computed tomography (BCT). Additionally, the impact of tissue elemental compositions from two databases were compared. Monte Carlo (MC) simulations were performed with the MC-GPU code to obtain the 3D glandular dose distribution (GDD) for each case considered with the mean glandular dose (MGD) fixed at 4 mGy (to facilitate comparisons). RESULTS: The GDD within the breast is more uniform for CEDM and BCT compared to DM and DBT. For large breasts and high VGF, the ratio between the minimum/maximum glandular dose to MGD is 0.12/4.02 for DM and 0.46/1.77 for BCT; the corresponding results for a small breast and low VGF are 0.35/1.98 (DM) and 0.63/1.42 (BCT). The elemental compositions of skin, adipose and glandular tissue have a considerable impact on the MGD, with variations up to 30% compared to the baseline. The inclusion of tissues other than glandular and adipose within the breast has a minor impact on MGD, with differences below 2%. Variations in the final compressed breast thickness alter the shape of the GDD, with a higher compression resulting in a more uniform GDD. CONCLUSIONS: For a constant MGD, the GDD varies with imaging modality and breast compression. Elemental tissue compositions are an important factor for obtaining MGD values, being a source of systematic uncertainties in MC simulations and, consequently, in breast dosimetry.

Medical student wellbeing during COVID-19: a qualitative study of challenges, coping strategies, and sources of support.

BACKGROUND: Medical students face challenges to their mental wellbeing and have a high prevalence of mental health problems. During training, they are expected to develop strategies for dealing with stress. This study investigated factors medical students perceived as draining and replenishing during COVID-19, using the 'coping reservoir' model of wellbeing. METHODS: In synchronous interactive pre-recorded webinars, 78 fourth-year medical students in the UK responded to reflective prompts. Participants wrote open-text comments on a Padlet site. Responses were analysed using reflexive thematic analysis. RESULTS: Analysis identified five themes. COVID-19 exacerbated academic pressures, while reducing the strategies available to cope with stress. Relational connections with family and friends were affected by the pandemic, leading to isolation and reliance on housemates for informal support. Relationships with patients were adversely affected by masks and telephone consultations, however attending placement was protective for some students' wellbeing. Experiences of formal support were generally positive, but some students experienced attitudinal and practical barriers. CONCLUSIONS: This study used a novel methodology to elicit medical students' reflections on their mental wellbeing during COVID-19. Our findings reinforce and extend the 'coping reservoir' model, increasing our understanding of factors that contribute to resilience or burnout. Many stressors that medical students typically face were exacerbated during COVID-19, and their access to coping strategies and support were restricted. The changes to relationships with family, friends, patients, and staff resulted in reduced support and isolation. Recognising the importance of relational connections upon medical students' mental wellbeing can inform future support.

Generation and comparison of 3D dosimetric reference datasets for COMS eye plaque brachytherapy using model-based dose calculations.

PURPOSE: A joint Working Group of the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) was created to aid in the transition from the AAPM TG-43 dose calculation formalism, the current standard, to model-based dose calculations. This work establishes the first test cases for low-energy photon-emitting brachytherapy using model-based dose calculation algorithms (MBDCAs). ACQUISITION AND VALIDATION METHODS: Five test cases are developed: (1) a single model 6711 125 I brachytherapy seed in water, 13 seeds (2) individually and (3) in combination in water, (4) the full Collaborative Ocular Melanoma Study (COMS) 16 mm eye plaque in water, and (5) the full plaque in a realistic eye phantom. Calculations are done with four Monte Carlo (MC) codes and a research version of a commercial treatment planning system (TPS). For all test cases, local agreement of MC codes was within ∼2.5% and global agreement was ∼2% (4% for test case 5). MC agreement was within expected uncertainties. Local agreement of TPS with MC was within 5% for test case 1 and ∼20% for test cases 4 and 5, and global agreement was within 0.4% for test case 1 and 10% for test cases 4 and 5. DATA FORMAT AND USAGE NOTES: Dose distributions for each set of MC and TPS calculations are available online (https://doi.org/10.52519/00005) along with input files and all other information necessary to repeat the calculations. POTENTIAL APPLICATIONS: These data can be used to support commissioning of MBDCAs for low-energy brachytherapy as recommended by TGs 186 and 221 and AAPM Report 372. This work additionally lays out a sample framework for the development of test cases that can be extended to other applications beyond eye plaque brachytherapy.

Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously.

Human naïve pluripotent stem cells (hnPSCs) can generate integrated models of blastocysts termed blastoids upon switch to inductive medium. However, the underlying mechanisms remain obscure. Here we report that self-renewing hnPSCs spontaneously and efficiently give rise to blastoids upon three dimensional (3D) suspension culture. The spontaneous blastoids mimic early stage human blastocysts in terms of structure, size, and transcriptome characteristics and are capable of progressing to post-implantation stages. This property is conferred by the glycogen synthase kinase-3 (GSK3) signalling inhibitor IM-12 present in 5iLAF self-renewing medium. IM-12 upregulates oxidative phosphorylation-associated genes that underly the capacity of hnPSCs to generate blastoids spontaneously. Starting from day one of self-organization, hnPSCs at the boundary of all 3D aggregates dedifferentiate into E5 embryo-like intermediates. Intermediates co-express SOX2/OCT4 and GATA6 and by day 3 specify trophoblast fate, which coincides with cavity and blastoid formation. In summary, spontaneous blastoid formation results from 3D culture triggering dedifferentiation of hnPSCs into earlier embryo-like intermediates which are then competent to segregate blastocyst fates.

Haralick texture analysis for microdosimetry: characterization of Monte Carlo generated 3D specific energy distributions.

Objective.Explore the application of Haralick textural analysis to 3D distributions of specific energy (energy imparted per unit mass) scored in cell-scale targets considering varying mean specific energy (absorbed dose), target volume, and incident spectrum.Approach.Monte Carlo simulations are used to generate specific energy distributions in cell-scale water voxels ((1µm)3-(15µm)3) irradiated by photon sources (mean energies: 0.02-2 MeV) to varying mean specific energies (10-400 mGy). Five Haralick features (homogeneity, contrast, entropy, correlation, local homogeneity) are calculated using an implementation of Haralick analysis designed to reduce sensitivity to grey level quantization and are interpreted using fundamental radiation physics.Main results.Haralick measures quantify differences in 3D specific energy distributions observed with varying voxel volume, absorbed dose magnitude, and source spectrum. For example, specific energy distributions in small (1-3µm) voxels with low magnitudes of absorbed dose (10 mGy) have relatively high measures of homogeneity and local homogeneity and relatively low measures of contrast and entropy (all relative to measures for larger voxels), reflecting the many voxels with zero specific energy in an otherwise sporadic distribution. With increasing target size, energy is shared across more target voxels, and trends in Haralick measures, such as decreasing homogeneity and increasing contrast and entropy, reflect characteristics of each 3D specific energy distribution. Specific energy distributions for sources of differing mean energy are characterized by Haralick measures, e.g. contrast generally decreases with increasing source energy, correlation and homogeneity are often (not always) higher for higher energy sources.Significance.Haralick texture analysis successfully quantifies spatial trends in 3D specific energy distributions characteristic of radiation source, target size, and absorbed dose magnitude, thus offering new avenues to quantify microdosimetric data beyond first order histogram features. Promising future directions include investigations of multiscale tissue models, targeted radiation therapy techniques, and biological response to radiation.