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Intranuclear inclusions present in the brains of patients with Fragile X-associated tremor/ataxia syndrome (FXTAS) have historically been difficult to study due to their location and scarcity. The recent finding that these particles autofluoresce has complicated the use of immunofluorescence techniques, but also offers new opportunities for purification. We have ascertained the features of the autofluorescence, including its excitation/emission spectrum, similarities and differences compared with lipofuscin autofluorescence, and its presence/absence under various fixation, mounting and UV light exposure conditions. Immunofluorescence at various wavelengths was conducted to determine which conditions are ideal for minimizing autofluorescence confounds. We also present a technique for autofluorescence-based sorting of FXTAS inclusions using flow cytometry, which will allow researchers in the field to purify inclusions more successfully for unbiased analyses.

Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation repeat expansion (55–200 CGG repeats) in the 5′ noncoding region of the FMR1 gene. Solitary intranuclear inclusions within FXTAS neurons and astrocytes constitute a hallmark of the disorder, yet our understanding of how and why these bodies form is limited. Here, we have discovered that FXTAS inclusions emit a distinct autofluorescence spectrum, which forms the basis of a novel, unbiased method for isolating FXTAS inclusions by preparative fluorescence-activated cell sorting (FACS). Using a combination of autofluorescence-based FACS and liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based proteomics, we have identified more than two hundred proteins that are enriched within the inclusions relative to FXTAS whole nuclei. Whereas no single protein species dominates inclusion composition, highly enriched levels of conjugated small ubiquitin-related modifier 2 (SUMO 2) protein and p62/sequestosome-1 (p62/SQSTM1) protein were found within the inclusions. Many additional proteins involved with RNA binding, protein turnover, and DNA damage repair were enriched within inclusions relative to total nuclear protein. The current analysis has also allowed the first direct detection, through peptide sequencing, of endogenous FMRpolyG peptide, the product of repeat-associated non-ATG (RAN) translation of the FMR1 mRNA. However, this peptide was found only at extremely low levels and not within whole FXTAS nuclear preparations, raising the question whether endogenous RAN products exist at quantities sufficient to contribute to FXTAS pathogenesis. The abundance of the inclusion-associated ubiquitin- and SUMO-based modifiers supports a model for inclusion formation as the result of increased protein loads and elevated oxidative stress leading to maladaptive autophagy. These results highlight the need to further investigate FXTAS pathogenesis in the context of endogenous systems.

Abstract There are millions of river barriers worldwide, ranging from wooden locks to concrete dams, many of which form associated impoundments to store water in small ponds or large reservoirs. Besides their benefits, there is growing recognition of important environmental and social trade-offs related to these artificial structures. However, global datasets describing their characteristics and geographical distribution are often biased towards particular regions or specific applications, such as hydropower dams affecting fish migration, and are thus not globally consistent. Here, we present a new river barrier and reservoir database developed by the Global Dam Watch (GDW) consortium that integrates, harmonizes, and augments existing global datasets to support large-scale analyses. Data curation involved extensive quality control processes to create a single, globally consistent data repository of instream barriers and reservoirs that are co-registered to a digital river network. Version 1.0 of the GDW database contains 41,145 barrier locations and 35,295 associated reservoir polygons representing a cumulative storage capacity of 7,420 km3 and an artificial terrestrial surface water area of 304,600 km2.

Abstract Background Sequencing and annotating genomes of non-model organisms helps to understand genome architecture, the genetic processes underlying species traits, and how these genes have evolved in closely-related taxa, among many other biological processes. However, many metazoan groups, such as the extremely diverse molluscs, are still underrepresented in the number of sequenced and annotated genomes. Although sequencing techniques have recently improved in quality and quantity, molluscs are still neglected due to difficulties in applying standardized protocols for obtaining genomic data. Results In this study, we present the chromosome-level genome assembly and annotation of the sacoglossan sea slug species Elysia timida, known for its ability to store the chloroplasts of its food algae. In particular, by optimizing the long-read and chromosome conformation capture library preparations, the genome assembly was performed using PacBio HiFi and Arima HiC data. The scaffold and contig N50s, at 41.8 Mb and 1.92 Mb, respectively, are approximately 30-fold and fourfold higher compared to other published sacoglossan genome assemblies. Structural annotation resulted in 19,904 protein-coding genes, which are more contiguous and complete compared to publicly available annotations of Sacoglossa with respect to metazoan BUSCOs. We found no evidence for horizontal gene transfer (HGT), i.e. no photosynthetic genes encoded in the sacoglossan nucleus genome. However, we detected genes encoding polyketide synthases in E. timida, indicating that polypropionates are produced. HPLC–MS/MS analysis confirmed the presence of a large number of polypropionates, including known and yet uncharacterised compounds. Conclusions We can show that our methodological approach helps to obtain a high-quality genome assembly even for a "difficult-to-sequence" organism, which may facilitate genome sequencing in molluscs. This will enable a better understanding of complex biological processes in molluscs, such as functional kleptoplasty in Sacoglossa, by significantly improving the quality of genome assemblies and annotations.

Abstract Background Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data. Results An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae. Conclusions Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.

Abstract Introduction The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. Methods This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. Results Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p

Abstract Background At the time of the COVID-19 pandemic, devastating incidents increased due to frequent oxygen administration to patients. The dangers associated with the use of oxygen, especially through local enrichments and formation of “oxygen clouds”, have been well understood for years. Nevertheless, dramatic incidents continue to occur, since fire hazard increases exponentially with oxygen concentrations above 23%. Rescue helicopters are at a particular high risk, because of technical reasons such as oxygen use in a very small space, surrounded by kerosene lines, electronic relays and extremely hot surfaces. Methods In this study three different sized rescue helicopter models (Airbus H135, H145 and MD902) were examined. Oxygen enrichment in the cabin was measured with an oxymeter during a delivery rate of 15 l/min constant flow for 60 min. Furthermore, the clearance of the enriched atmosphere was tested in different situations and with different ventilation methods. To make the airflow visible, a fog machine was used to fill the helicopter cabin. Results Oxygen accumulation above 21% was detected in every helicopter. After 10–15 min, the critical 23% threshold was exceeded in all three aircrafts. The highest concentration was detected in the smallest machine (MD902) after 60 min with 27.4%. Moreover, oxygen clouds persisted in the rear and the bottom of the aircrafts, even when the front doors were opened. This was most pronounced in the largest aircraft, the H145 from Airbus Helicopters. Complete and rapid removal of elevated oxygen concentrations was achieved only by cross-ventilation within 1 min. Conclusions Oxygen should be handled with particular care in rescue helicopters. Adapted checklists and precautions can help to prevent oxygen accumulation, and thus, fatal incidents. To our knowledge, this is the first study, which analyzed oxygen concentrations in different settings in rescue helicopters.

Abstract Virtual meetings are widespread in organizations despite being perceived as fatiguing; a phenomenon also known as Zoom fatigue. Research suggests that Zoom fatigue is stronger when the camera is on, potentially influencing individuals to conform to majority opinions during professional online meetings. Two preregistered studies were conducted to explore the relationships between camera use, Zoom fatigue, social presence, and conformity. Study 1 involved 287 participants describing a professional online meeting in terms of the content discussed as well as the study variables. Study 2 involved 64 participants in an experimentally manipulated online meeting (camera on vs. off), focusing on a personnel selection task. We measured how many times participants changed their answers to match the majority and how this was related to Zoom fatigue and self-reported conformity. Results from both studies indicated that camera use was not related to either conformity or Zoom fatigue. Despite not finding the presumed mediation effect, the studies showed a clear link between fatigue and conformity. The results explain the emergence of conformity in online meetings and provide practical information for the design of video conferences.

Abstract Background Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer’s disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting. Methods Fifty cognitively unimpaired adults (Age 68 ± 6.2 years, 58% female, 46% Aβ-positive) completed remote, tablet-based speech assessments (i.e., picture description, journal-prompt storytelling, verbal fluency tasks) for five days. The testing paradigm was repeated after 2–3 weeks. Acoustic speech features were automatically extracted from the voice recordings, and mean scores were calculated over the 5-day period. We assessed feasibility by adherence rates and usability ratings on the System Usability Scale (SUS) questionnaire. Test-retest reliability was examined with intraclass correlation coefficients (ICCs). We investigated the associations between acoustic features and Aβ-pathology, using linear regression models, adjusted for age, sex and education. Results The speech assessment was feasible, indicated by 91.6% adherence and usability scores of 86.0 ± 9.9. High reliability (ICC ≥ 0.75) was found across averaged speech samples. Aβ-positive individuals displayed a higher pause-to-word ratio in picture description (B = -0.05, p = 0.040) and journal-prompt storytelling (B = -0.07, p = 0.032) than Aβ-negative individuals, although this effect lost significance after correction for multiple testing. Conclusion Our findings support the feasibility and reliability of multi-day remote assessment of speech acoustics in cognitively unimpaired individuals with and without Aβ-pathology, which lays the foundation for the use of speech biomarkers in the context of early AD.

Abstract Background Despite pain control being a top priority in end-of-life care, pain continues to be a troublesome symptom and comprehensive data on pain prevalence and pain relief in patients with different diagnoses are scarce. Methods The Swedish Register of Palliative Care (SRPC) was used to retrieve data from 2011 to 2022 about pain during the last week of life. Data were collected regarding occurrence of pain, whether pain was relieved and occurrence of severe pain, to examine if pain differed between patients with cancer, heart failure, chronic obstructive pulmonary disease (COPD) and dementia. Binary logistic regression models adjusted for sex and age were used. Results A total of 315 000 patients were included in the study. Pain during the last week of life was more commonly seen in cancer (81%) than in dementia (69%), heart failure (68%) or COPD (57%), also when controlled for age and sex, p

Abstract The basal structure of the bacterial flagellum includes a membrane embedded MS-ring (formed by multiple copies of FliF) and a cytoplasmic C-ring (composed of proteins FliG, FliM and FliN). The SRP-type GTPase FlhF is required for directing the initial flagellar protein FliF to the cell pole, but the mechanisms are unclear. Here, we show that FlhF anchors developing flagellar structures to the polar landmark protein HubP/FimV, thereby restricting their formation to the cell pole. Specifically, the GTPase domain of FlhF interacts with HubP, while a structured domain at the N-terminus of FlhF binds to FliG. FlhF-bound FliG subsequently engages with the MS-ring protein FliF. Thus, the interaction of FlhF with HubP and FliG recruits a FliF-FliG complex to the cell pole. In addition, the modulation of FlhF activity by the MinD-type ATPase FlhG controls the interaction of FliG with FliM-FliN, thereby regulating the progression of flagellar assembly at the pole.

Abstract Background Salinity, exacerbated by rising sea levels, is a critical environmental cue affecting freshwater ecosystems. Predicting ecosystem structure in response to such changes and their implications for the geographical distribution of arthropod disease vectors requires further insights into the plasticity and adaptability of lower trophic level species in freshwater systems. Our study investigated whether populations of the mosquito Culex pipiens, typically considered sensitive to salt, have adapted due to gradual exposure. Methods Mesocosm experiments were conducted to evaluate responses in life history traits to increasing levels of salinity in three populations along a gradient perpendicular to the North Sea coast. Salt concentrations up to the brackish–marine transition zone (8 g/l chloride) were used, upon which no survival was expected. To determine how this process affects oviposition, a colonization experiment was performed by exposing the coastal population to the same concentrations. Results While concentrations up to the currently described median lethal dose (LD50) (4 g/l) were surprisingly favored during egg laying, even the treatment with the highest salt concentration was incidentally colonized. Differences in development rates among populations were observed, but the influence of salinity was evident only at 4 g/l and higher, resulting in only a 1-day delay. Mortality rates were lower than expected, reaching only 20% for coastal and inland populations and 41% for the intermediate population at the highest salinity. Sex ratios remained unaffected across the tested range. Conclusions The high tolerance to salinity for all key life history parameters across populations suggests that Cx. pipiens is unlikely to shift its distribution in the foreseeable future, with potential implications for the disease risk of associated pathogens. Graphical Abstract

Abstract Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl − 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.

Abstract Background Currently, the data regarding the impact of prehospital postcardiac arrest anesthesia on target hemodynamic and ventilatory parameters of early postresuscitation care and recommendations on its implementation are rare. The present study examines the incidence and impact of prehospital postcardiac arrest anesthesia on hemodynamic and ventilatory target parameters of postresuscitation care. Methods In this multicentre observational study between 2019 and 2021 unconscious adult patients after out-of-hospital-cardiac arrest with the presence of a return-of-spontaneous circulation until hospital admission were included. Primary endpoint was the application of postarrest anesthesia. Secondary endpoints included the medication group used, predisposing factors to its implementation, and its influence on achieving target parameters of postresuscitation care (systolic blood pressure: ≥ 100 mmHg, etCO2:35–45 mmHg, SpO2: 94–98%) at hospital handover. Results During the study period 2,335 out-of-hospital resuscitations out of 391,305 prehospital emergency operations (incidence: 0.58%; 95% CI 0.54–0.63) were observed with a return of spontaneous circulation to hospital admission in 706 patients (30.7%; 95% CI 28.8–32.6; female: 34.3%; age:68.3 ± 14.2 years). Postcardiac arrest anesthesia was performed in 482 patients (68.3%; 95% CI 64.7–71.7) with application of hypnotics in 93.4% (n = 451), analgesics in 53.7% (n = 259) and relaxants in 45.6% (n = 220). Factors influencing postcardiac arrest sedation were emergency care by an anesthetist (odds ratio: 2.10; 95% CI 1.34–3.30; P

The ecologically valuable and unique natural and cultural landscapes of protected areas are popular nature tourism destinations. From a spatial perspective, travellers visit protected areas by moving from their place of origin to the destination for a temporary stay. This paper analyses the travel distances of day visitors and overnight guests to German national parks and biosphere reserves. National parks position themselves as both regional and national destinations. In contrast, biosphere reserve tourism is more regionally concentrated due to the proximity of biosphere reserves to urban centres, which are the primary places of origin for visitors. On average, visitors travel 278.6 km by car to visit a national park, taking 172.1 minutes (02:52 hours). Opting for public transport increases the average travel distance to 312.5 km, with a travel time of 284.5 minutes (04:43 hours). Visitors to German biosphere reserves travel 208.7 km by car, requiring 134.7 minutes (02:15 hours). When using public transport to visit biosphere reserves, the average distance increases to 234.0 km, with a travel time of 239.1 minutes (03:59 hours). The automated, GIS-supported distance analyses offer an innovative approach for assessing nature tourism catchment areas and the accessibility of protected areas, serving as a basis for effective spatial planning, development, and regional marketing.

Addressing disparities is crucial for enhancing population health, ensuring health security, and fostering resilient health systems. Disparities in acute care surgery (trauma, emergency general surgery, and surgical critical care) have been well documented and the magnitude of inequities demand an intentional, organized, and effective response. As part of its commitment to achieve high-quality, equitable care in all aspects of acute care surgery, the American Association for the Surgery of Trauma convened an expert panel at its eigty-second annual meeting in September 2023 to discuss how to take action to work towards health equity in acute care surgery practice. The panel discussion framed contemporary disparities in the context of historic and political injustices, then identified targets for interventions and potential action items in health system structure, health policy, the surgical workforce, institutional operations and quality efforts. We offer a four-pronged approach to address health inequities: identify, reduce, eliminate, and heal disparities, with the goal of building a healthcare system that achieves equity and justice for all.

BackgroundAlthough tobacco use has significantly declined in the general population, traditional tobacco use treatment uptake and success rates remain disproportionately low among people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native. Technology-based interventions (TBIs) for tobacco use are promising alternatives to traditional tobacco use treatments. ObjectiveThis scoping review aims to investigate the extent to which the use of digital TBIs in tobacco use treatment research promotes health equity among people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native. MethodsThis scoping review identifies US-based studies (between January 2000 and March 2021) that enlist TBIs for tobacco use treatment and include people who identify as African American/Black, Hispanic/Latina/o, and American Indian/Alaska Native at ≥50% of the sample when combined; features studies that are also race and ethnicity conscious; and highlights health equity–promoting insights from included studies. ResultsIn 85% (22/26) of the studies, the largest proportion of the sample was African American/Black, most participants had low socioeconomic status, and recruitment was most commonly from medical settings. In total, 58% (15/26) of the studies were race and ethnicity conscious, and 67% (10/15) of these studies sought to partner with potential end users. An array of TBIs were represented; however, SMS text messaging was most prevalent. Most TBIs were combined with other evidence-based intervention components (eg, nicotine replacement therapy). Approximately one-third of the studies (8/26, 31%) required participants to have their own device or internet access. The majority were underpowered to detect substantial differences. ConclusionsThe modest number of studies, particularly for persons who identify as Hispanic/Latina/o and American Indian/Alaska Native, demonstrates the limited application of TBIs for tobacco use and that additional research is needed to determine the extent to which TBIs for tobacco use promote health equity among these populations. International Registered Report Identifier (IRRID)RR2-10.2196/34508

Abstract Background Physical activity (PA), sleep and sedentary time are now recognised as mutually exclusive and exhaustive parts of the 24‐h day—if PA decreases, time spent sleeping, being sedentary or both must increase so that all components equate to 24 h. Recent advances in time‐use epidemiology suggest that we should not consider time‐use domains (PA, sleep and sedentary time) in isolation from each other, but in terms of a composition—the mix of time‐use domains across the 24‐h day. While interrelated daily activities are known to be important in the management of diabetes mellitus, few studies have investigated the interrelated daily activities in people with an active diabetes‐related foot ulcer (DFU) and their impact on important outcomes such as wound severity, blood glucose control and health‐related quality of life (HRQoL). This feasibility study aims to determine the acceptability and practicality of measuring 24‐h use of time data in people with a DFU and its associations on important outcome measures for this population. Methods Participants wore a wrist‐worn accelerometer for two weeks and completed demographic and HRQoL questionnaires. Outcomes were participant engagement, reported levels of study burden and value and compositional data analysis as a methodological approach for evaluating 24‐h use of time data. Results Twenty‐six participants reported low levels of study burden and rated the study value highly. The protocol appears feasible in terms of recruitment (81%) and retention rate (86%). On average, participants were relatively sedentary spending 747, 172 and 18 min in sedentary time, light physical activity and moderate‐to‐vigorous activity, respectively. Sleep appeared adequate with participants obtaining an average of 485 min, but quality of sleep was notably poor with average sleep efficiency of 75%. Compositional data analysis was able to quantify the integrated associations of 24‐h use of time with HRQoL. Conclusion The protocol provides an acceptable method to collect 24‐h use of time data in people with a DFU. Efforts to consider and analyse PA as part of a 24‐h activity composition may provide holistic and realistic understandings of PA in this clinical population.

Objective To perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa.Design A systematic review of study methods.Data sources MEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022.Eligibility criteria Primary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa.Data extraction and synthesis Studies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings.Results Our search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs’ potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers.Conclusion Impact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs’ effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation.PROSPERO registration number CRD42018083816.

Background: Early cardiopulmonary resuscitation and defibrillation is key to increasing survival following an out-of-hospital-cardiac-arrest (OHCA). However, automated external defibrillators (AEDs) are used in a very small percentage of cases. Despite large numbers of AEDs in the community, the absence of a unified system for registering their locations across the UK’s ambulance services may have resulted in missed opportunities to save lives. Therefore, representatives from the resuscitation community worked alongside ambulance services to develop a single repository for data on the location of AEDs in the UK. Methods: A national defibrillator network, “The Circuit”, was developed by the British Heart Foundation in collaboration with the Association of Ambulance Chief Executives, the UK ambulance services, the Resuscitation Council UK and St John Ambulance. The database allows individuals or organisations to record information about AED location, accessibility, and availability. The database synchronises with ambulance computer aided dispatch systems to provide UK ambulance services with real-time information on the nearest, available AED. Results: The Circuit was successfully rolled out to all 14 UK ambulance services. Since 2019, 82,108 AEDs have been registered. Of the AED data collected by The Circuit, 54% were not previously registered to any ambulance service, and are therefore new registrations. Conclusion: The Circuit provides ambulance services with a single point of access to AED locations in the UK. Since the launch of the system the number of defibrillators registered has doubled. Linking the Circuit data with patient outcome data will help understand whether improving the accessibility to AEDs is associated with increased survival.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

Crocins comprise a family of hydrophilic carotenoids with pharmacological properties that are produced in significant quantities in stigma of Crocus sativus. Although the biosynthesis pathway of crocins has been sufficiently elucidated, there is a paucity of information regarding how transcription factors (TFs) regulate crocin biosynthesis in various stigma developmental stages. WRKY TFs play a role in modulating carotenoid/apocarotenoid metabolism. To provide an overview of the WRKY family in Crocus sativus (CsWRKY) and characterize candidate CsWRKY TFs involved in the biosynthesis of crocins, CsWRKY genes were identified from RNA-sequenced stigma at different developmental stages. A phylogenetic analysis was performed to characterize their evolutionary interrelatedness. A coexpression analysis of CsWRKY genes and crocin biosynthesis-related genes was performed. A quantitative real-time polymerase chain reaction was used to corroborate the expression level of CsWRKY TFs in various tissue and at different developmental stages. A total of 34 CsWRKY TFs were identified from the stigma of C. sativus. The CsWRKY TFs, together with their orthologs from Arabidopsis, were clustered into group I, II, or III following phylogenetic analysis. A correlation analysis revealed that the expressions of the TFs CsWRKY1, CsWRKY2, CsWRKY8, CsWRKY10, CsWRKY15, and CsWRKY28 were strongly related to the expression of crocin biosynthesis-related genes CsBCH, CsCCD2L, CsALDH, and CsUGT. CsWRKY2, CsWRKY15, and CsWRKY28 exhibited identical motifs and were stratified into group IId. Transcript levels of candidate CsWRKY genes were higher in stigma than in other tissues and were proportional to the crocin content.

IntroductionBesides societal and governmental actions to mitigate greenhouse gases, individual behavioral changes are also urgently needed to limit global temperature rise. However, these individual changes have proven to be difficult to achieve in the general population.MethodsWe conducted a systematic review in five electronic databases with the aim of systematically depicting the content of interventions that promote climate-friendly behavior in individuals and households in high- and upper-middle-income countries.ResultsWe included 25 studies. The analyses included identification of the used Behavior Change Techniques (BCTs) and comparison of their promise ratio. Across our three outcome categories energy consumption, water consumption, and mobility the most frequently used BCT categories are not the ones that are most promising in terms of behavior change.DiscussionBased on these results, our recommendation for climate change mitigation interventions is to include components that provide concrete instructions on how to perform the desired behavior (shaping knowledge), setting goals and commitments (goals and planning), substituting undesired behavior, and practicing desired behavior (repetition and substitution). Other reviews with similar aims use different wordings, definitions, or degrees of detail in their intervention component labelling which makes it difficult to compare the results. We recommend to use a standardized classification system, like the BCT taxonomy in combination with the promise ratio, which this study has shown to be a suitable tool to classify applied intervention techniques and give an indication of successful techniques.

In this paper, we argue that the recent debates andproclaimed crises in psychology are partly due to a reflection deficit and the reductionist understanding of psychology as exclusively a science. For this reason, we introduce Psychological Humanities as a novel interdisciplinary approach that defines psychology as its object of investigation and opens a field of reflection. Although the study of psychological topics with an orientation toward the humanities is not new, either within or outside of psychology, we argue for the introduction of the collective term Psychological Humanities for four reasons: (1) the definition of Psychological Humanities does more justice to central psychological subject areas such as subjectivity, (2) it serves as a common term of interconnectedness and visibility, (3) it resonates with new reflective fields in related disciplines, such as the medical humanities, and (4) it is more consistent with intersubjective practice in applied psychology. In what follows, we present our approach to Psychological Humanities, developed at the University of Lübeck. Our model differentiates between two fundamental views: a view from the outside on the discipline of psychology and its contexts (e.g., through history, cultural studies, and ethics) and a view from the inside on psychology (e.g., through theoretical psychology, critical psychologies, or epistemology of psychology).

Abstract Background Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if energy intake is not controlled. Diazoxide choline extended-release (DCCR) tablets have previously been evaluated for their effects on hyperphagia and other behavioral complications of people with PWS in a Phase 3 placebo-controlled study of participants with PWS, age 4 and older with hyperphagia (C601) and in an open label extension study, C602. Methods To better understand the longer-term impact of DCCR, a cohort from PATH for PWS, a natural history study that enrolled participants with PWS age 5 and older, who met the C601 age, weight and baseline hyperphagia inclusion criteria and had 2 hyperphagia assessments ≥ 6 months apart, were compared to the C601/C602 cohort. Hyperphagia was measured using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT, range 0–36). The primary analysis used observed values with no explicit imputation of missing data. A sensitivity analysis was conducted in which all missing HQ-CT assessments in the C601/C602 cohort were assigned the highest possible value (36), representing the worst-case scenario. Other behavioral changes were assessed using the Prader-Willi Syndrome Profile questionnaire (PWSP). Results Relative to the PATH for PWS natural history study cohort, the DCCR-treated C601/C602 cohort showed significant improvements in HQ-CT score at 26 weeks (LSmean [SE] -8.3 [0.75] vs. -2.5 [0.43], p

Abstract Background Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polyps removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. Design and methods We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-month follow-up, and Life Simple7 (LS7)—a cardiovascular disease (CVD) risk score—at 6 months and 1 year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. Discussion Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. Trial registration NCT05174286; clinicaltrials.gov; August 31st, 2023

Abstract Aims Acute mitral regurgitation (MR) in the setting of myocardial infarction (MI) may be the result of papillary muscle rupture (PMR). This condition is associated with high morbidity and mortality. We aim to evaluate the feasibility of transcatheter edge‐to‐edge mitral valve repair (TEER) in this acute setting. Methods and results We analysed data from the International Registry of MitraClip in Acute Mitral Regurgitation following acute Myocardial Infarction (IREMMI) of 30 centres in Europe, North America, and the middle east. We included patients with post‐MI PMR treated with TEER as a salvage procedure, and we evaluated immediate and 30‐day outcomes. Twenty‐three patients were included in this analysis (9 patients suffered complete papillary muscle rupture, 9 partial and 5 chordal rupture). The patients' mean age was 68 ± 14 years. Patients were at high surgical risk with median EuroSCORE II 27% (IQR 16, 28) and 20 out of 23 (87% were in cardiogenic shock). All patients were treated with vasopressors, and 17 out of 23 patients required mechanical support. TEER procedure was performed on the median 6 days after the index MI date IQR (3, 11). Procedural success was achieved in 87% of patients. The grade of MR was significantly decreased after the procedure. MR reduction to 0 or 1 + was achieved in 13 patients (57%), to 2 + in 7 patients (30%), P

Abstract The Mars Sample Return mission intends to retrieve a sealed collection of rocks, regolith, and atmosphere sampled from Jezero Crater, Mars, by the NASA Perseverance rover mission. For all life-related research, it is necessary to evaluate water availability in the samples and on Mars. Within the first Martian year, Perseverance has acquired an estimated total mass of 355 g of rocks and regolith, and 38 μmoles of Martian atmospheric gas. Using in-situ observations acquired by the Perseverance rover, we show that the present-day environmental conditions at Jezero allow for the hydration of sulfates, chlorides, and perchlorates and the occasional formation of frost as well as a diurnal atmospheric-surface water exchange of 0.5–10 g water per m2 (assuming a well-mixed atmosphere). At night, when the temperature drops below 190 K, the surface water activity can exceed 0.5, the lowest limit for cell reproduction. During the day, when the temperature is above the cell replication limit of 245 K, water activity is less than 0.02. The environmental conditions at the surface of Jezero Crater, where these samples were acquired, are incompatible with the cell replication limits currently known on Earth.

Acoustic focusing of particle flow in microfluidics has been shown to be an efficient tool for particle separation for various chemical and biomedical applications. The mechanism behind the method is the selective effect of the acoustic radiation force on distinct particles. In this way, they can be selectively focused and separated. The technique can also be applied under stationary conditions, i.e., in the absence of fluid flows. In this study, the manipulation of self-propelled particles, such as Janus particles, in an acoustofluidic setup was investigated. In experiments with self-propelled Janus particles and passive beads, we explored the interplay between self-propulsion and the acoustic radiation force. Our results demonstrated unusual and potentially useful effects such as selective trapping, escape, and assisted escape in binary mixtures of active and passive particles. We also analyzed various aspects related to the behavior of Janus particles in acoustic traps in the presence and absence of flows.

Abstract The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

Abstract Objective Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups. Results Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined.

Abstract To describe migration-related phenomena, we need to reflect on the terminology and choose the most adequate one that allows us to determine whether migration is the (main) cause of a phenomenon, a consequence, or even unrelated and misattributed. We argue that the use of such terminology in quantitative and experimental research is often flawed because of its differentiated adoption in legal, political, or scientific contexts. To illustrate our argument, we focus on two commonly used terms, ‘second generation’ and ‘migration background’ to show that in many situations these terms do not accurately describe the population we study. In part, the terms imply a false homogeneity, focus on deficits, and perpetuate differences regarding national belonging where there may be structural reasons and other aspects, such as social class, that lie at the heart of observed differences. With a particular focus on quantitative research, we use survey evidence and a principled literature search, to show that both researchers and the general population often identify immigrants in terms of ethnic origin — even though the term has its own pitfalls. We conclude that quantitative research should avoid reproducing state-created terminology and instead look beyond the strict field of immigration to consider other systems of classification like gender, ethnicity, language, or social class to reduce the negative attributes ascribed to non-citizens.

Abstract Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p

Abstract Background Besides motor impairments, up to 90% of the children and adolescents with unilateral cerebral palsy (uCP) present with somatosensory impairments in the upper limb. As somatosensory information is of utmost importance for coordinated movements and motor learning, somatosensory impairments can further compromise the effective use of the impaired upper limb in daily life activities. Yet, intervention approaches specifically designated to target these somatosensory impairments are insufficiently investigated in children and adolescents with uCP. Therefore, the aim of this randomized controlled trial (RCT) is to compare the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP, who experience somatosensory impairments in the upper limb. We will further explore potential behavioral and neurological predictors of therapy response. Methods A parallel group, evaluator-blinded, phase-II, single-center RCT will be conducted for which 50 children and adolescents with uCP, aged 7 to 15 years, will be recruited. Participants will be randomized to receive 3 weekly sessions of 45 minutes of either somatosensory discrimination therapy or upper limb motor therapy for a period of 8 weeks. Stratification will be performed based on age, manual ability, and severity of tactile impairment at baseline. Sensorimotor upper limb function will be evaluated at baseline, immediately after the intervention and after 6 months follow-up. The primary outcome measure will be bimanual performance as measured with the Assisting Hand Assessment. Secondary outcomes include a comprehensive test battery to objectify somatosensory function and measures of bimanual coordination, unimanual motor function, and goal attainment. Brain imaging will be performed at baseline to investigate structural brain lesion characteristics and structural connectivity of the white matter tracts. Discussion This protocol describes the design of an RCT comparing the effectiveness of somatosensory discrimination therapy and dose-matched motor therapy to improve sensorimotor upper limb function in children and adolescents with uCP. The results of this study may aid in the selection of the most effective upper limb therapy, specifically for children and adolescents with tactile impairments. Trial registration ClinicalTrials.gov (NCT06006065). Registered on August 8, 2023.

Background In occupational therapy and -science positive aspects of occupation are highlighted. Recently, this discourse has been questioned, as it might leave out occupations – referred to as unilluminated occupations (UO) – that hold value to people, without fitting the positive ideal.Aim To translate UO into Danish and to examine how occupational therapists (OTs) view and address UO.Methods A survey developed in USA was translated into Danish and distributed to OTs across Denmark. We added questions on the Danish wording of the concepts, including a content validity index (CVI). Data was subjected to a descriptive analysis.Results The respondents agreed that OTs must include examining the purpose and meaning of UO, however without having a responsibility to support performing these UO. The applied translation: high risk (risikable), unhealthy (usunde), unethical (uetiske), immoral (umoralske), and unacceptable (uacceptable) were deemed relevant in Danish, established by CVIs on 0.72–0.90.Conclusions and significance Although most respondents were positive towards examining and acknowledging clients’ purpose and meaning of UO, no clear consensus when addressing UO in interventions was seen. Further research might shed light on ways to approach UO both in assessment and intervention. The Danish terms appeared relevant to encompass UO.

ABSTRACTThe higher order structure (HOS) of monoclonal antibodies (mAbs) is an important quality attribute with strong contribution to clinically relevant biological functions and drug safety. Due to the multi-faceted nature of HOS, the synergy of multiple complementary analytical approaches can substantially improve the understanding, accuracy, and resolution of HOS characterization. In this study, we applied one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy coupled with chemometric analysis, as well as circular dichroism (CD), differential scanning calorimetry (DSC), and fluorescence spectroscopy as orthogonal methods, to characterize the impact of methionine (Met) oxidation on the HOS of an IgG1 mAb. We used a forced degradation method involving concentration-dependent oxidation by peracetic acid, in which Met oxidation is site-specifically quantified by liquid chromatography-mass spectrometry. Conventional biophysical techniques report nuanced results, in which CD detects no change to the secondary structure and little change in the tertiary structure. Yet, DSC measurements show the destabilization of Fab and Fc domains due to Met oxidation. More importantly, our study demonstrates that 1D and 2D NMR and chemometric analysis can provide semi-quantitative analysis of chemical modifications and resolve localized conformational changes with high sensitivity. Furthermore, we leveraged a novel 15N-Met labeling technique of the antibody to directly observe structural perturbations at the oxidation sites. The NMR methods described here to probe HOS changes are highly reliable and practical in biopharmaceutical characterization.

Background: The number of patients who have survived cancer has increased substantially owing to improved cancer treatment. This has reinforced the need for effective strategies for follow-up cancer care in general practice. Aim: To investigate the organisation of follow-up cancer care in Danish general practice and to analyse GPs’ self-assessment of competences regarding patients who have survived cancer and late effects. Design & setting: A total of 500 Danish general practices were invited to a web-based survey. Method: Questions comprised organisation of follow-up cancer care, and GPs’ self-assessment of their competences in follow-up care and evaluation of late effects. Covariates considered included sex, age, seniority, and practice type. Analyses were conducted using descriptive statistics and multivariable logistic regression models. Results: Some 28% of the GPs reported systematic organisation of follow-up cancer care in their clinic. More than half of the GPs assessed themselves as competent in evaluating mental sequelae, existential considerations, and the impact on comorbidities. In contrast, only 19% and 33% of GPs reported competences in sexual and physical sequelae, respectively. Female GPs were less likely to report competences regarding physical and mental sequelae as well as sexual disturbances, and GPs from partnership practices were more likely to report competence in assessing mental sequelae. Conclusion: Fewer than one in three general practices have organised systematic follow-up cancer care and GPs assess their competence as low with respect to physical sequelae and sexual challenges. This emphasises the need for more systematic organisation and focus on knowledge of late effects in general practice.

BackgroundChildren with craniopharyngiomas (CPs) typically suffer from a life-long chronic disease. The younger the child, the more vulnerable the maturing brain is to invasive therapies such as surgery or radiotherapy. Therefore, treatment modalities facilitating avoidance or delay of invasive therapies are beneficial for these patients. In the last decade, intracystic injection of interferon alfa-2a or alfa-2b evolved as a treatment of choice based on efficacy and minor toxicity. However, the drug is no longer available internationally. After an extensive pharmacological review, peginterferon alfa-2a was identified as the agent with closest similarity.MethodsA retrospective case series is described, including five patients treated with intracystic peginterferon alfa-2a for cystic CP according to an innovative care protocol. After initial CP cyst aspiration, peginterferon alfa-2a was injected once per week via an Ommaya reservoir for 6 weeks followed by response assessment with MRI.ResultsPatients’ age ranged from 4 to 54 years (four patients

Summary: Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p

Objective: To describe clinicoradiological features and surgical outcomes in a series of nine patients with rhino-orbito-cerebral mucormycosis (ROCM) who presented with Pott's puffy tumor (ROCM-PPT) Methods: The records of nine patients with ROCM-PPT seen between March 2020 and December 2021 were analysed. Clinical features, radiology, histopathology, operative findings, management and outcome were noted. Frontal sinus pneumatisation and outflow tract configuration was compared between patients and controls with ROCM and no PPT. Results: ROCM-PPT was diagnosed in 9 of 284 (3.2 %) patients with ROCM seen during the study period. There were six (66.7 %) males and the median age was 54 (IQR 46–60) years. Eight (88.9 %) patients had diabetes mellitus and seven (77.8 %) had been COVID-19 positive. Radiological features of osteomyelitis, subperiosteal abscess formation and dural enhancement were seen in all patients. No significant differences in pneumatisation or frontal sinus outflow tract configuration were noted between patients and controls. All patients underwent a craniectomy with frontal bone debridement and frontal sinus exteriorisation. All patients were treated with anti-fungal agents for several months. All patients had symptomatic improvement at a median follow-up of 21 (IQR 18–23) months. Repeat CT/MRI scans showed disease regression/resolution in six out of eight (75 %) patients with follow-up imaging, and stable disease in two others. Conclusions: ROCM-PPT is a rare, delayed complication of mucormycosis that was seen in larger numbers during the recent COVID-19 pandemic. Aggressive debridement of osteomyelitic bone and antifungal therapy results in a good outcome.