Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.

Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.

Inclusion of deuterated glycopeptides provides increased sequence coverage in hydrogen/deuterium exchange mass spectrometry analysis of SARS-CoV-2 spike glycoprotein.

RATIONALE: Hydrogen/deuterium exchange mass spectrometry (HDX-MS) can provide precise analysis of a protein's conformational dynamics across varied states, such as heat-denatured versus native protein structures, localizing regions that are specifically affected by such conditional changes. Maximizing protein sequence coverage provides high confidence that regions of interest were located by HDX-MS, but one challenge for complete sequence coverage is N-glycosylation sites. The deuteration of peptides post-translationally modified by asparagine-bound glycans (glycopeptides) has not always been identified in previous reports of HDX-MS analyses, causing significant sequence coverage gaps in heavily glycosylated proteins and uncertainty in structural dynamics in many regions throughout a glycoprotein. METHODS: We detected deuterated glycopeptides with a Tribrid Orbitrap Eclipse mass spectrometer performing data-dependent acquisition. An MS scan was used to identify precursor ions; if high-energy collision-induced dissociation MS/MS of the precursor indicated oxonium ions diagnostic for complex glycans, then electron transfer low-energy collision-induced dissociation MS/MS scans of the precursor identified the modified asparagine residue and the glycan's mass. As in traditional HDX-MS, the identified glycopeptides were then analyzed at the MS level in samples labeled with D2 O. RESULTS: We report HDX-MS analysis of the SARS-CoV-2 spike protein ectodomain in its trimeric prefusion form, which has 22 predicted N-glycosylation sites per monomer, with and without heat treatment. We identified glycopeptides and calculated their average isotopic mass shifts from deuteration. Inclusion of the deuterated glycopeptides increased sequence coverage of spike ectodomain from 76% to 84%, demonstrated that glycopeptides had been deuterated, and improved confidence in results localizing structural rearrangements. CONCLUSION: Inclusion of deuterated glycopeptides improves the analysis of the conformational dynamics of glycoproteins such as viral surface antigens and cellular receptors.

Examining the use, confidence, and barriers to follow Advanced Life Support in Obstetrics (ALSO) course guides in managing obstetric emergencies in Sudan.

BACKGROUND: The Advanced Life Support in Obstetrics (ALSO) course is a globally recognized interprofessional training program designed to assist healthcare professionals in acquiring and sustaining the necessary knowledge and skills to handle obstetric emergencies effectively. This survey aimed to assess the use, barriers, and confidence in using the ALSO course guidelines in managing obstetric emergencies in Sudan. METHODS: This descriptive cross-sectional study involved 103 physicians from the Sudan ALSO group in Sudan. A structured, close-ended questionnaire was distributed electronically to the participants. Data analysis was conducted using Statistical Package of Social Sciences Software version 26. RESULTS: More than half of the participants were specialists (54.4%). Although all respondents claimed to adhere to the ALSO guidelines for managing shoulder dystocia, a lower percentage followed them for neonatal resuscitation (75.0%) and maternal venous thrombosis management (68.9%). Only 62.1% of participants felt confident performing neonatal resuscitation. The main barriers to implementing the ALSO course guidelines were the respondents' preference for other guidelines and their belief that the guidelines were not applicable in their specific settings. CONCLUSION: The majority of participants displayed a high level of confidence, indicating a positive perception of the guide's effectiveness. However, there is room for improvement, particularly in areas such as neonatal resuscitation and forceps-assisted births, where confidence levels were lower. Addressing barriers, including the preference for other guidelines and the applicability of the guide in specific settings, is crucial to ensure widespread adoption. Refresher training programs, contextual adaptations, and the integration of guidelines may help overcome these barriers and enhance the overall implementation of the ALSO guide in managing obstetric emergencies in Sudan.

Retraining transplant pharmacy staff to reduce Medicare Part B prescription billing errors post-transplant.

BACKGROUND: Medicare Part B (MedB) imposes penalties for certain errors in prescription billing of post-transplant medications, which can greatly affect pharmacy revenue. To prevent MedB billing fines, pharmacy staff must be cognizant of specific MedB requirements. OBJECTIVE: This quality improvement project aimed to retrain certified pharmacy technicians (CPhTs) on common billing errors and evaluate changes in error rates and potential fines after retraining. We aimed to determine whether retraining CPhTs minimizes MedB prescription billing errors and reduces potential fines owed by the Vanderbilt Transplant Pharmacy (VTP) to the Centers for Medicare and Medicaid Services (CMS). METHODS: This was a single-center, quality improvement study including post-transplant patients with at least one MedB prescription billing error who filled prescriptions through VTP. All CPhTs involved in MedB prescription billing received retraining focused on the top 3 errors in MedB billing identified at VTP: early refills, missing relationship of caller to patient and residence of patient on order documentation, or no day supply remaining recorded on the order file. Retraining consisted of developing a training checklist, testing current knowledge levels, individualized nonpunitive coaching based on technician specific errors, and retesting for knowledge retention. Outcomes included the number of prescriptions with at least one MedB prescription billing error and the projected amount of dollars fined owing to errors recorded during the 3 months before and 3 months after retraining. RESULTS: Fourteen CPhTs received retraining. Average refill too soon errors decreased by 37.5% (10.7% vs. 6.7%), average missing relationship by 21.7% (7.7% vs. 6%), and day supply errors by 39.7% (1.7% vs. 1%). Error reductions equaled a 28.2% decrease (approximately $12,700) in potential fines. CONCLUSION: Retraining focused on MedB billing error successfully reduced error frequency and fines from CMS. MedB billing error fines can be costly for pharmacies dispensing high-cost medications; therefore, identifying common errors and training staff can be useful and financially prudent.

Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

Analysis of the N-glycosylation profiles of the spike proteins from the Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2.

N-Glycosylation plays an important role in the structure and function of membrane and secreted proteins. Viral proteins used in cell entry are often extensively glycosylated to assist in protein folding, provide stability, and shield the virus from immune recognition by its host (described as a "glycan shield"). The SARS-CoV-2 spike protein (S) is a prime example, having 22 potential sites of N-glycosylation per protein protomer, as predicted from the primary sequence. In this report, we conducted mass spectrometric analysis of the N-glycosylation profiles of recombinant spike proteins derived from four common SARS-CoV-2 variants classified as Variant of Concern, including Alpha, Beta, Gamma, and Delta along with D614G variant spike as a control. Our data reveal that the amino acid substitutions and deletions between variants impact the abundance and type of glycans on glycosylation sites of the spike protein. Some of the N-glycosylation sequons in S show differences between SARS-CoV-2 variants in the distribution of glycan forms. In comparison with our previously reported site-specific glycan analysis on the S-D614G and its ancestral protein, glycan types on later variants showed high similarity on the site-specific glycan content to S-D614G. Additionally, we applied multiple digestion methods on each sample, and confirmed the results for individual glycosylation sites from different experiment conditions to improve the identification and quantification of glycopeptides. Detailed site-specific glycan analysis of a wide variety of SARS-CoV-2 variants provides useful information toward the understanding of the role of protein glycosylation on viral protein structure and function and development of effective vaccines and therapeutics.

Experiences of caregivers and individuals living with traumatic brain injury in accessing health information: a qualitative investigation.

BACKGROUND/PURPOSE: Rehabilitation and treatment of chronic symptoms of traumatic brain injury (TBI) present life-long challenges. This qualitative study aimed to understand the experience of individuals with TBI and caregivers in finding and using health information and to understand their interest in participating in research. METHODS: Participants were recruited through hospital listservs, websites, social media, and word of mouth from across the US. A qualitative constructivism research method was used to analyze responses from semi-structured interviews with 24 individuals, 11 with TBI and 13 caregivers. RESULTS: Three major themes emerged from the analyses: 1) processes and resources for finding TBI-related health information, 2) reliability of information, and 3) participation in research. Study participants described using the internet, consulting with healthcare professionals, reading research articles, and seeking out information from other individuals with TBI or caregivers to search for information. Participants also shared their experiences related to evaluating the reliability of information and the impact of individuals with TBI and caregivers participating on research teams. CONCLUSION: Participants identified various needs in finding relevant health information and highlighted gaps in searching for and using health information. Participants identified an overarching need for improved dissemination of information that is both accessible and reliable.

Risk Factors for Surgical Site Infection after Operative Fixation of Acetabular Fractures: Is Psoas Density a Useful Metric?

BACKGROUND: Surgical site infection (SSI) occurs in 5% to 7% of patients undergoing operative fixation of acetabular fractures, with reported risk factors including longer operative duration, increased blood loss, pelvic artery embolization, and concurrent abdominal organ injury, among others. Psoas muscle density is a measure of muscle quality and, as a metric for sarcopenia and/or nutrition status, has been associated with poor outcomes such as mortality across multiple surgical specialties. To date, psoas muscle density has not been explored for its associations with SSI in acetabular fracture patients.Questions/purposes (1) Is decreased psoas muscle density, as measured by Hounsfield units, associated with an increased SSI risk after acetabular fracture fixation? (2) What patient, operative, and hospital variables are associated with an increased SSI risk after acetabular fracture fixation? METHODS: Between 2012 to 2017, surgeons performed 684 acetabular ORIF procedures at one level I trauma center. Of those, 8% (56 of 684) did not meet inclusion criteria, leaving 92% (n = 628) for analysis in this study. The median (range) follow-up duration was 12 months (0.5-77). Patient demographics, comorbidities, operative and in-hospital variables, and psoas muscle density measured using preoperative pelvic CT images-acquired for all operative acetabular fracture patients-were analyzed. SSI was defined by positive culture results obtained during irrigation and débridement. Overall, 7% (42 of 628) of patients had an SSI. A multivariable regression analysis was performed to identify independent risk factors. Sensitivity analysis was performed with minimum follow-up set at 3 months and 6 months. RESULTS: There was no difference in the mean psoas muscle density between patients with SSI (50.9 ± 10.2 Hounsfield units [HUs]) and those who did not have an SSI within 1 year of open reduction and internal fixation (51.4 ± 8.1 HUs) (mean difference: 0.5 [95% confidence interval -2.34 to 3.32]; p = 0.69). Four variables were independently associated with an increased risk of SSI: increased operative time (1.04 [95% CI 1.00 to 1.07]; p = 0.03), estimated blood loss (1.08 [95% CI 1.02 to 1.14]; p = 0.01), female sex (2.34 [95% CI 1.19 to 4.60]; p = 0.01), and intravenous drug use (3.95 [95% CI 1.51 to 10.33]; p = 0.01). Sensitivity analysis showed no change in results using either 3-month or 6-month minimum follow-up. CONCLUSIONS: Risk factors for SSI after acetabular fixation include female sex, intravenous drug use, prolonged operative times, and increased intraoperative blood loss. Although the density of the psoas muscle may be a surrogate for nutritional markers, it was not associated with SSI in our patients with acetabular fractures. Thus, it is not useful for risk assessment of SSI in the general population with acetabular fracture; however, future studies with larger sample sizes of patients older than 60 years may re-investigate this marker for SSI risk. Contrary to the results of previous studies, pelvic artery embolization, intraoperative blood transfusion, and intensive care unit stay did not increase the risk of SSI; however, we may have been underpowered to detect differences in these secondary endpoints. Future large, multisite studies may be needed to address these conflicting results more definitively. LEVEL OF EVIDENCE: Level III, therapeutic study.

Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020.

Several Italian towns are under lockdown to contain the COVID-19 outbreak. The level of transmission reduction required for physical distancing interventions to mitigate the epidemic is a crucial question. We show that very high adherence to community quarantine (total stay-home policy) and a small household size is necessary for curbing the outbreak in a locked-down town. The larger the household size and amount of time in the public, the longer the lockdown period needed.

Machine learning for radiomics-based multimodality and multiparametric modeling.

Due to the recent developments of both hardware and software technologies, multimodality medical imaging techniques have been increasingly applied in clinical practice and research studies. Previously, the application of multimodality imaging in oncology has been mainly related to combining anatomical and functional imaging to improve diagnostic specificity and/or target definition, such as positron emission tomography/computed tomography (PET/CT) and single-photon emission CT (SPECT)/CT. More recently, the fusion of various images, such as multiparametric magnetic resonance imaging (MRI) sequences, different PET tracer images, PET/MRI, has become more prevalent, which has enabled more comprehensive characterization of the tumor phenotype. In order to take advantage of these valuable multimodal data for clinical decision making using radiomics, we present two ways to implement the multimodal image analysis, namely radiomic (handcrafted feature) based and deep learning (machine learned feature) based methods. Applying advanced machine (deep) learning algorithms across multimodality images have shown better results compared with single modality modeling for prognostic and/or prediction of clinical outcomes. This holds great potentials for providing more personalized treatment for patients and achieve better outcomes.

Validation and comparison of the Arabic versions of GOHAI and OHIP-14 in patients with and without denture experience.

BACKGROUND: The assessment of oral heath related quality of life (OHRQoL) for complete denture wearers according to a participant's subjective perception may provide an indication of the adaptive capacity of the individual. The aim of this study was to compare and assess the validation of two quality of life measures, the Oral Health Impact Profile-14 (OHIP-14) and Geriatric Oral Health Assessment Index (GOHAI), in patients with and without previous denture experience. METHODS: A total of 69 elders (36 male and 34 female; mean age, 63 years) from Dental Clinics of the University of Khartoum and the National University in Sudan, with and without previous denture experience, were included in the study. OHRQoL was assessed using two Arabic-translated questionnaires (OHIP-14 and GOHAI) before and after complete denture therapy. Global self-ratings of oral and general health were obtained, and denture satisfaction was assessed using the Denture Satisfaction questionnaire. RESULTS: Both tools had significant correlations with self-rating oral health in patients without denture experience (P < 0.05). However, no significant correlations were found in patients with denture experience. There were significant differences between pre-and post-treatment total scores with both the GOHAI and OHIP-14 (P < 0.001). Responsiveness to treatment using GOHAI and OHIP-14 revealed overall mean effect size higher in patients without (1.49) and (0.83) than those with previous denture experience (0.89) and (0.60), respectively. However, neither tool could detect significant differences between patients with and without denture experience (P > 0.05). CONCLUSION: Greater improvements of OHRQoL after complete denture therapy were observed in participants without than those with previous denture experience. The Arabic-translated versions of GOHAI and OHIP-14 can be regarded as effective measures for assessing treatment outcomes of complete denture therapy.

Accelerated partial breast irradiation (APBI): are breath-hold and volumetric radiation therapy techniques useful?

BACKGROUND: In a selective group of patients accelerated partial breast irradiation (APBI) might be applied after conservative breast surgery to reduce the amount of irradiated healthy tissue. The role of volumetric modulated arc therapy (VMAT) and voluntary moderately deep inspiration breath-hold (vmDIBH) techniques in further reducing irradiated healthy--especially heart--tissue is investigated. MATERIAL AND METHODS: For 37 partial breast planning target volumes (PTVs), three-dimensional conformal radiotherapy (3D-CRT) (3-5 coplanar or non-coplanar 6 and/or 10 MV beams) and VMAT (two partial 6 MV arcs) plans were made on CTs acquired in free-breathing (FB) and/or in vmDIBH. Dose-volume parameters for the PTV, heart, lungs, and breasts were compared. RESULTS: Better dose conformity was achieved with VMAT compared to 3D-CRT (conformity index 1.24±0.09 vs. 1.49±0.20). Non-PTV ipsilateral breast receiving ≥50% of the prescribed dose was on average reduced by 28% in VMAT plans compared to 3D-CRT plans. Mean heart dose (MHD) reduced from 2.0 (0.1-5.1) Gy in 3D-CRT(FB) to 0.6 (0.1-1.6) Gy in VMAT(vmDIBH). VMAT is beneficial for MHD reduction if MHD with 3D-CRT exceeds 0.5Gy. Cardiac dose reduction as a result of VMAT increases with increasing initial MHD, and adding vmDIBH reduces the cardiac dose further. Mean dose to the ipsilateral lung decreased from 3.7 (0.7-8.7) to 1.8 (0.5-4.0) Gy with VMAT(vmDIBH) compared to 3D-CRT(FB). VMAT resulted in a slight increase in the contralateral breast dose (DMean) always remaining <1.9 Gy). CONCLUSIONS: For APBI patients, VMAT improves PTV dose conformity and delivers lower doses to the ipsilateral breast and lung compared to 3D-CRT. This goes at the cost of a slight but acceptable increase of the contralateral breast dose. VMAT reduces cardiac dose if MHD exceeds 0.5 Gy for 3D-CRT. Adding vmDIBH results in a further reduction of heart and ipsilateral lung dose.

Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT.

PURPOSE: To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. MATERIAL AND METHODS: Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. RESULTS: Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. CONCLUSIONS: On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol.

Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile.

SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding in proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including the ectodomain, receptor-binding domain, and N-terminal domain. Additionally, mutagenesis and pull-down assays reveal the role of glycosylation of a specific sequon (N149); furthermore, the correlation of MD simulation and HDX-MS identified several high-dynamic areas of the spike proteins. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.

War and education: the attacks on medical schools amidst ongoing armed conflict, Sudan 2023.

BACKGROUND: War results in widespread destruction of a country's infrastructure, healthcare facilities, and educational institutions. This study aims to assess the attacks on medical schools amidst the ongoing conflict in Sudan. METHODS: A descriptive cross-sectional study was conducted across 58 medical schools located in the states of Khartoum, Darfur, and Kordofan. Data on attacks between April 15, 2023, and July 15th 2023, were collected using online data collection form. RESULTS: All medical schools in conflict areas were included in the study. More than half (58.6%) of these medical schools were attacked. Private schools, constituting the majority of the study sample, were the most frequently attacked (70.6%). Of these, 52.9% were located in Khartoum city. More than one form of attack was reported in 64.7% of the affected schools. Looting occurred in 73.5% of the attacked faculties, while 67.6% of them were converted into military bases. Despite these challenges, 60.3% of the schools in the conflict zone managed to restore the educational process through online learning and collaboration with other institutions. CONCLUSION: During a three-month period of warfare, most medical schools within conflict zones were attacked. This emphasizes the vulnerability of medical education institutions during war and highlights the urgent need of the Ministry of Higher Education interventions to provide leadership, support, and oversight for the educational process in medical schools across the country.

Violence in Sudan: A Looming Public Health Disaster.

Sudan's ongoing conflict, rooted in colonial-era policies and resource competition, has led to widespread displacement, poverty, and social service breakdowns. The escalating power struggle between the Sudanese Army Forces (SAF) and the paramilitary Rapid Support Forces (RSF) exacerbates the humanitarian crisis by severely undermining the nation's health services and infrastructure. This leads to long-lasting social and economic consequences, creating a need for a coordinated response from national and international organizations to provide emergency healthcare, rebuild infrastructure, and train and retain healthcare workers. Moreover, the recent takeover of a National Public Health Laboratory in Khartoum, which contains dangerous biological material, is considered extremely dangerous. The expulsion of technicians and power cuts prevent the proper management of biological materials (e.g., polio, measles, and cholera isolates). This editorial sheds light on the deep-seated repercussions of the conflict in Sudan, with a specific focus on the toll it takes on health services and infrastructure. It calls for an all-encompassing, synergistic approach that places the health and welfare of impacted communities at the forefront. Through concerted collaboration between national entities and the global community, there lies the potential to pave the way for recuperation, fortitude, and enduring stability in regions ravaged by conflict.

Prioritizing children's mental health amidst Sudan's humanitarian crisis: policy recommendations for immediate action.

The humanitarian crisis precipitated by the ongoing conflict in Sudan poses profound risks to the health and welfare of the country's children. This paper explores essential policy interventions to safeguard child mental health services under these challenging circumstances. Crucial strategies include enhancing healthcare accessibility for children and their caregivers, promoting education, and improving household living conditions. Additionally, it is vital to provide improved access to information about nutritious food and strengthen health systems in areas directly exposed to conflict. Cooperation with international aid organizations is paramount to delivering medical supplies to functioning health facilities. The paper also recommends partnerships with local non-governmental and humanitarian organizations to execute public health programs effectively. These multi-faceted policy measures underscore the importance of a comprehensive response to ensure the health and well-being of children amid the turmoil in Sudan. Through these strategies, we aim to provide a blueprint for policymakers and humanitarian organizations to mitigate the devastating impacts of the conflict on the country's most vulnerable population.

Development and optimisation of a preclinical cone beam computed tomography-based radiomics workflow for radiation oncology research.

Background and purpose: Radiomics features derived from medical images have the potential to act as imaging biomarkers to improve diagnosis and predict treatment response in oncology. However, the complex relationships between radiomics features and the biological characteristics of tumours are yet to be fully determined. In this study, we developed a preclinical cone beam computed tomography (CBCT) radiomics workflow with the aim to use in vivo models to further develop radiomics signatures. Materials and methods: CBCT scans of a mouse phantom were acquired using onboard imaging from a small animal radiotherapy research platform (SARRP, Xstrahl). The repeatability and reproducibility of radiomics outputs were compared across different imaging protocols, segmentation sizes, pre-processing parameters and materials. Robust features were identified and used to compare scans of two xenograft mouse tumour models (A549 and H460). Results: Changes to the radiomics workflow significantly impact feature robustness. Preclinical CBCT radiomics analysis is feasible with 119 stable features identified from scans imaged at 60 kV, 25 bin width and 0.26 mm slice thickness. Large variation in segmentation volumes reduced the number of reliable radiomics features for analysis. Standardization in imaging and analysis parameters is essential in preclinical radiomics analysis to improve accuracy of outputs, leading to more consistent and reproducible findings. Conclusions: We present the first optimised workflow for preclinical CBCT radiomics to identify imaging biomarkers. Preclinical radiomics has the potential to maximise the quantity of data captured in in vivo experiments and could provide key information supporting the wider application of radiomics.

Rumination and the displacement of aggression in United Kingdom gang-affiliated youth.

The concept of gang aggression oftentimes elicits images of brutal intergang violence. In reality, gang-related aggression can vary widely, can have various motivations and causal factors, and includes interpersonal as well as intergroup aggression. This study examined the tendency of UK youth to engage in displaced aggression (aggression aimed at undeserving targets) and examined the relationship among gang affiliation, ruminative thought, and aggression levels. Students in three London schools were asked to complete a questionnaire that assessed levels of gang affiliation, rumination about aversive events, and a tendency to engage in displaced aggression. Our analyses found a three-way interaction between gang affiliation, rumination, and gender, such that males who were high in affiliation and rumination had the greatest tendency to displace aggression toward innocent others. Additionally, it was shown that rumination could account for a significant part of the correlation between gang affiliation and displaced aggression. Furthermore, regression analyses showed that even after controlling for trait aggression, anger, hostility, and irritability, rumination remained a significant predictor of displaced aggression. The implications for understanding gang-related aggression and for conducting future research in this area were discussed.

Access, Utilization, and Implementation of Research Among Rehabilitation Nurses: A Qualitative Study.

PURPOSE: This study aimed to understand rehabilitation nurses' perceptions of research information, related barriers, and avenues for future research, specifically in those caring for individuals with burn injury, spinal cord injury, or traumatic brain injury. DESIGN: Qualitative semistructured interviews were conducted. METHODS: Eighteen interviews were conducted. A thematic network approach identified codes and developed basic, organizing, and global themes. RESULTS: Researchers identified factors that facilitated research uptake, determined organizational structures that support research culture, and described nurse engagement with literature. CONCLUSIONS: Although participants desired to engage with the research literature, they identified barriers including time constraints, heavy workloads, and lack of access. To facilitate research uptake, research must be easily accessible, be easily digestible, and include clinical practice recommendations. Research must expand its scope to address issues relevant to the rehabilitation population. CLINICAL RELEVANCE: Our findings may be used to drive improvements in research competence, facilitate knowledge translation, and support evidence-based practice among rehabilitation nurses.