Isolation and characterization of nettle (Urtica dioica L.) seed proteins: Conversion of underutilized by-products of the edible oil industry into food emulsifiers.

This study aimed to upcycle a byproduct of the edible oil industry, cold-pressed nettle seed meal (CPNSM), into a plant-based emulsifier, thereby increasing the sustainability of the food system. The protein content of the nettle seed protein (NSP) powder was 48.3% with glutamic acid (16.6%), asparagine (10.7%), and arginine (9.7%) being the major amino acids. NSPs had a denaturation temperature of 66.6 °C and an isoelectric point of pH 4.3. They could be used as emulsifiers to form highly viscous coarse corn oil-in-water emulsions (10% oil, 4% NSP). Nevertheless, 10-fold diluted emulsions exhibited rapid creaming under different pH (2-9), salt (0-500 mM NaCl) and temperature (>40 °C) conditions, but they were relatively stable to aggregation. Our findings suggest that NSPs could be used as emulsifiers in highly viscous or gelled foods, like dressings, sauces, egg, cheese, or meat analogs.

Adaptive designs in public health: Vaccine and cluster randomized trials go Bayesian.

Clinical trials in public health-particularly those conducted in low- and middle-income countries-often involve communicable and non-communicable diseases with high disease burden and unmet needs. Trials conducted in these regions often are faced with resource limitations, so improving the efficiencies of these trials is critical. Adaptive trial designs have the potential to save trial time and resources and reduce the number of patients receiving ineffective interventions. In this paper, we provide a detailed account of the implementation of vaccine and cluster randomized trials within the framework of Bayesian adaptive trials, with emphasis on computational efficiency and flexibility with regard to stopping rules and allocation ratios. We offer an educated approach to selecting prior distributions and a data-driven empirical Bayes method for plug-in estimates for nuisance parameters.

Matched vs Nonmatched Placebos in a Randomized Trial of COVID-19 Treatments.

Importance: Matched placebo interventions are complex and resource intensive. Recent evidence suggests matched placebos may not always be necessary. Previous studies have predominantly evaluated potential bias of nonmatched placebos (ie, differing on dose, frequency of administration, or formulation) in pain and mental health, but to date no systematic examination has been conducted in infectious disease. Objective: To test for differences between nonmatched and matched placebo arms with respect to clinical outcome measures across multiple therapeutics for COVID-19. Design, Setting, and Participants: In a comparative effectiveness research study, a post hoc analysis was conducted of data on individual patients enrolled in a large, multiarm, platform randomized clinical trial in symptomatic adult outpatients with COVID-19 between January 15, 2021, to September 28, 2023, in which the outcomes of both matched and nonmatched placebo groups were reported. Bayesian and frequentist covariate-adjusted techniques were compared with 7 intervention-placebo pairs. Exposures: Seven matched and nonmatched placebo pairs (for a total of 7 comparisons) were evaluated throughout the primary platform trial. Comparisons were made between treatment and its associated matched (concurrent) placebo, as well as with nonmatched placebo (alone and in combination) assessed at a similar time point. Main Outcomes and Measures: Outcomes assessed included hospitalizations, EuroQol 5-Dimension 5-level scores, and PROMIS Global-10 scores. Results: A total of 7 intervention-control pairs (N = 2684) were assessed, including 1620 (60.4%) women, with mean (SD) age, 47 (15.2) years; the most common comorbidities were obesity (41.9%) and hypertension (37.9%). In a meta-analysis with decoupled SEs, accounting for overlapping placebo patients, the overall odds ratio (OR) of nonmatched compared with matched placebo was 1.01 (95% credible interval, 0.77-1.32), with posterior probability of equivalence, defined as 0.8 ≤ OR ≤ 1.2 (a deviation from perfect equivalence ie, OR = 1, by no more than 0.2) of 85.4%, implying no significant difference. Unadjusted analysis of the event rate difference between all nonmatched and matched placebo groups did not identify any notable differences across all 7 treatment-placebo combinations assessed. Similar analysis that was conducted for patient-reported quality of life outcomes did not yield statistically significant differences. Conclusions and Relevance: In this post hoc study of a randomized clinical platform trial, pooling matched and nonmatched placebo patient data did not lead to inconsistencies in treatment effect estimation for any of the investigational drugs. These findings may have significant implications for future platform trials, as the use of nonmatched placebo may improve statistical power, or reduce barriers to placebo implementation.

Assessing the performance of group-based trajectory modeling method to discover different patterns of medication adherence.

It is well known that medication adherence is critical to patient outcomes and can decrease patient mortality. The Pharmacy Quality Alliance (PQA) has recognized and identified medication adherence as an important indicator of medication-use quality. Hence, there is a need to use the right methods to assess medication adherence. The PQA has endorsed the proportion of days covered (PDC) as the primary method of measuring adherence. Although easy to calculate, the PDC has however several drawbacks as a method of measuring adherence. PDC is a deterministic approach that cannot capture the complexity of a dynamic phenomenon. Group-based trajectory modeling (GBTM) is increasingly proposed as an alternative to capture heterogeneity in medication adherence. The main goal of this paper is to demonstrate, through a simulation study, the ability of GBTM to capture treatment adherence when compared to its deterministic PDC analogue and to the nonparametric longitudinal K-means. A time-varying treatment was generated as a quadratic function of time, baseline, and time-varying covariates. Three trajectory models are considered combining a cat's cradle effect, and a rainbow effect. The performance of GBTM was compared to the PDC and longitudinal K-means using the absolute bias, the variance, the c-statistics, the relative bias, and the relative variance. For all explored scenarios, we find that GBTM performed better in capturing different patterns of medication adherence with lower relative bias and variance even under model misspecification than PDC and longitudinal K-means.

The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast.

BACKGROUND: ER positive breast cancer is currently targeted using various endocrine therapies. Despite the proven therapeutic efficacy, resistance to the drug and reoccurrence of tumor appears to be a complication that many patients deal with. Molecular pathways underlying the development of resistance are being widely studied. METHODS AND RESULTS: In this study, using four established endocrine resistant breast cancer (ERBC) cell lines, we characterized CXCL1 as a secreted factor in crosstalk between ERBC cells and fibroblasts. Protein array revealed upregulation of CXCL1 and we confirmed the CXCL1 expression by real-time qRT-PCR and U-Plex assay. Co-culturing ERBC cells with fibroblasts enhanced the cell growth and migration compared to monoculture. The crosstalk of ERBC cells with fibroblasts significantly activates ERK/MAPK signaling pathway while reparixin, CXCR1/2 receptor inhibitor, attenuates the activity. Reparixin displayed the ERBC cell growth inhibition and the combination treatment with reparixin and CDK4/6 inhibitor (palbociclib and ribociclib) increased these inhibitory effect. CONCLUSIONS: Taken together, our study implicates CXCL1 as a critical role in ERBC growth and metastasis via crosstalk with fibroblast and cotargeting CXCR1/2 and CDK4/6 could potentially overcome endocrine resistant breast cancer.

Comparison of survival prediction models for bone metastases of the extremities following surgery.

Aims: This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods: This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results: The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion: State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E.

Sarm1 knockout prevents type 1 diabetic bone disease in females independent of neuropathy.

Patients with diabetes have a high risk of developing skeletal diseases accompanied by diabetic peripheral neuropathy (DPN). In this study, we isolated the role of DPN in skeletal disease with global and conditional knockout models of sterile-α and TIR-motif-containing protein-1 (Sarm1). SARM1, an NADase highly expressed in the nervous system, regulates axon degeneration upon a range of insults, including DPN. Global knockout of Sarm1 prevented DPN, but not skeletal disease, in male mice with type 1 diabetes (T1D). Female wild-type mice also developed diabetic bone disease but without DPN. Unexpectedly, global Sarm1 knockout completely protected female mice from T1D-associated bone suppression and skeletal fragility despite comparable muscle atrophy and hyperglycemia. Global Sarm1 knockout rescued bone health through sustained osteoblast function with abrogation of local oxidative stress responses. This was independent of the neural actions of SARM1, as beneficial effects on bone were lost with neural conditional Sarm1 knockout. This study demonstrates that the onset of skeletal disease occurs rapidly in both male and female mice with T1D completely independently of DPN. In addition, this reveals that clinical SARM1 inhibitors, currently being developed for treatment of neuropathy, may also have benefits for diabetic bone through actions outside of the nervous system.

Lower Plasma Amyloid Beta - 42 Levels Associated With Worse Survival in Patients With Glioma.

BACKGROUND/AIM: Glioma is often refractory. The accumulation of amyloid beta (Aß) in the brain is commonly associated with Alzheimer's disease (AD), but there are studies suggesting that Aß has tumor suppressor potential. The aim of this study was to identify a novel, non-invasive candidate biomarker for histological prediction and prognostic assessment of glioma. PATIENTS AND METHODS: Serum was prepared from blood samples collected preoperatively from 48 patients with WHO grade II-IV glioma between October 2004 and December 2017 at a single tertiary institution. The concentration of Aß42 was measured using the SMCxPRO immunoassay (Merck). The clinical and histological characteristics of the patients, including molecular subtypes, were reviewed. RESULTS: The mean age of the patients was 52.2±12.5 years. The mean value of serum Aß42 concentration was 7.6±7.8 pg/ml in the anaplastic astrocytoma (WHO grade III) group and 6.4±6.5 pg/ml in the glioblastoma multiforme (WHO grade IV) group. The Negative epidermal growth factor receptor (EGFR) expression was associated with higher serum Aß42 levels (p=0.020). Kaplan-Meier analysis demonstrated that patients with high serum Aß42 (>11.78 pg/ml) had significantly longer progression-free survival (PFS) (p=0.038) and overall survival (OS) (p=0.018). CONCLUSION: This study investigated serum Aß42 levels as a potential biomarker for glioma. The results showed that low serum Aß42 levels were associated with EGFR expression and poor PFS and OS. Overall, these findings suggest a potential role of Aß42 as a prognostic marker in astrocytomas.

Developing the surgeon-machine interface: using a novel instance-segmentation framework for intraoperative landmark labelling.

Introduction: The utilisation of artificial intelligence (AI) augments intraoperative safety, surgical training, and patient outcomes. We introduce the term Surgeon-Machine Interface (SMI) to describe this innovative intersection between surgeons and machine inference. A custom deep computer vision (CV) architecture within a sparse labelling paradigm was developed, specifically tailored to conceptualise the SMI. This platform demonstrates the ability to perform instance segmentation on anatomical landmarks and tools from a single open spinal dural arteriovenous fistula (dAVF) surgery video dataset. Methods: Our custom deep convolutional neural network was based on SOLOv2 architecture for precise, instance-level segmentation of surgical video data. Test video consisted of 8520 frames, with sparse labelling of only 133 frames annotated for training. Accuracy and inference time, assessed using F1-score and mean Average Precision (mAP), were compared against current state-of-the-art architectures on a separate test set of 85 additionally annotated frames. Results: Our SMI demonstrated superior accuracy and computing speed compared to these frameworks. The F1-score and mAP achieved by our platform were 17% and 15.2% respectively, surpassing MaskRCNN (15.2%, 13.9%), YOLOv3 (5.4%, 11.9%), and SOLOv2 (3.1%, 10.4%). Considering detections that exceeded the Intersection over Union threshold of 50%, our platform achieved an impressive F1-score of 44.2% and mAP of 46.3%, outperforming MaskRCNN (41.3%, 43.5%), YOLOv3 (15%, 34.1%), and SOLOv2 (9%, 32.3%). Our platform demonstrated the fastest inference time (88ms), compared to MaskRCNN (90ms), SOLOV2 (100ms), and YOLOv3 (106ms). Finally, the minimal amount of training set demonstrated a good generalisation performance -our architecture successfully identified objects in a frame that were not included in the training or validation frames, indicating its ability to handle out-of-domain scenarios. Discussion: We present our development of an innovative intraoperative SMI to demonstrate the future promise of advanced CV in the surgical domain. Through successful implementation in a microscopic dAVF surgery, our framework demonstrates superior performance over current state-of-the-art segmentation architectures in intraoperative landmark guidance with high sample efficiency, representing the most advanced AI-enabled surgical inference platform to date. Our future goals include transfer learning paradigms for scaling to additional surgery types, addressing clinical and technical limitations for performing real-time decoding, and ultimate enablement of a real-time neurosurgical guidance platform.

Virtual student-led neuroscience conferencing: a UK multicentre prospective study investigating delegate outcomes and delivery mode.

BACKGROUND: Clinical neuroscience training programmes are becoming increasingly competitive to enter. UK university neuroscience societies act as a local environment for students to develop their career interests and provide portfolio building opportunities through hosting events such as annual conferences. Recently there has been a transition to more of these events being held online yet the impact of this, if any, remains unclear. This prospective study aimed to identify the impact of student-led neuroscience conferences on delegates and examine attitudes towards an online delivery approach. METHODS: Multi-centre prospective survey study using pre-conference, post-conference, and 6-month post-conference online questionnaires distributed at 6 virtual student-led neuroscience conferences in 2021. The questionnaires had five-domains: demographics, career aspirations, academic skillsets, an educational manipulation check (EMC) and mode of delivery preference. RESULTS: Nine hundred twenty-four surveys were completed across 559 conference attendances. 79.9% of delegates were medical students. Interest in a neuroscience career (p < 0.001), preparedness to undertake research (p < 0.001) and presentation (p < 0.001), as well as EMC scores (p < 0.001) increased immediately post conference. Most participants at 6 months post-attendance had completed an academic project (71.9%) or presentation (50.9%), although 88.8% were lost to follow up. Online format was preferred (65%) with reasons including elimination of travel and access to home facilities whilst lack of face-to-face interaction and engagement were recognised limitations. CONCLUSION: UK student-led online neuroscience conferences play a role in developing knowledge and may facilitate career interest, academic skillset and longer term portfolio building. A hybrid virtual and in-person experience would offer an ideal solution to future conferencing, providing options promoting engagement and interactivity whilst advocating sustainability, accessibility and widening participation.

Optimizing Protein Fiber Spinning to Develop Plant-Based Meat Analogs via Rheological and Physicochemical Analyses.

The substitution of meat products in the human diet with plant-based analogs is growing due to environmental, ethical, and health reasons. In this study, the potential of fiber-spinning technology was explored to spin protein fiber mimicking the structural element of meat muscle for the purpose of developing plant-based meat analogs. Overall, this approach involved extruding fine fibers and then assembling them into hierarchical fibrous structures resembling those found in whole muscle meat products. Considering the nutritional facts and to help build muscle fiber, soy protein, polysaccharide (pectin, xanthan gum, or carrageenan), plasticizer (glycerol), and water were used in the formulations to spin into fibers using an extruder with circular orifice dies. Extrudability and thermal and rheological properties were assessed to characterize the properties of the spun fiber. The extrusion trials showed that the presence of the polysaccharides increased the cohesiveness of the fibers. The properties of the fibers produced also depended on the temperature used during extrusion, varying from pasty gels to elastic strands. The extrudability of the fibers was related to the rheological properties (tan δ) of the formulations. This study demonstrated that fiber-spinning technology can be used to produce fibrous materials from plant-derived ingredients. However, the formulation and operating conditions must be optimized to obtain desirable physicochemical and functional attributes in the fibers produced.

National audit of pathways in epileptic seizure referrals (NAPIER): A national, multicentre audit of first seizure clinics throughout the UK and Ireland.

BACKGROUND: Current guidelines set clinical standards for the management of suspected first seizures and epilepsy. We aimed to assess if these standards are being met across first seizure clinics nationally, to describe variations in care and identify opportunities for service delivery improvement. METHODS: Multicentre audit assessing the care of adults (≥16 years) referred to first seizure clinics from 31st December 2019 going backwards (30 consecutive patients per centre). Patients with pre-existing diagnosis of epilepsy were excluded. Anonymised referral, clinic, and follow-up data are reported with descriptive statistics. RESULTS: Data provided for 727 patients from 25 hospitals in the UK and Ireland (median age 41 years [IQR 26-59], 52% males). Median time to review was 48 days (IQR 26-86), with 13.8% (IQR 3.3%-24.0%) of patients assessed within 2 weeks. Seizure recurrence was seen in 12.7% (IQR 6.6%-17.4%) of patients awaiting first appointment. Documentation for witness accounts and driving advice was evident in 85.0% (IQR 74.0%-100%) and 79.7% (IQR 71.2%-96.4%) of first seizure/epilepsy patients, respectively. At first appointment, discussion of sudden unexpected death in epilepsy was documented in 30.1% (IQR 0%-42.5%) of patients diagnosed with epilepsy. In epilepsy patients, median time to MRI neuroimaging was 37 days [IQR 22-56] and EEG was 30 days [IQR 19-47]. 30.4% ([IQR 0%-59.5%]) of epilepsy patients were referred to epilepsy nurse specialists. CONCLUSIONS: There is variability nationally in the documented care of patients referred to first seizure clinics. Many patients are facing delays to assessment with epilepsy specialists with likely subsequent impact on further management.

Follow Your Heart: Trials and Tribulations of Sir Terence English and the First Successful Heart Transplant in the United Kingdom.

The journey of heart transplantation in the United Kingdom (UK) has been marked by challenges and triumphs. Following a series of unsuccessful transplant attempts in 1968, a moratorium was imposed on the procedure. However, in 1979, Sir Terence English broke the national ban, by performing the UK's first successful heart transplant at Papworth Hospital. This achievement opened doors for advancements in heart and lung transplantation and established the Papworth programme as a world leader in the field. Sir Terence's legacy stands as a testament to the transformative power of determination, perseverance and teamwork in overcoming the moratorium, lack of financial support, difficult colleagues and the failure of his first transplant attempt. Through a comprehensive review of the literature, qualitative interviews and Sir Terence's personal contributions, this article provides an account of his trials and tribulations, aiming to inspire and encourage physicians, surgeons and scientists in their pursuit of innovation in the field of medicine.

Extending the vision of adaptive point-of-care platform trials to improve targeted use of drug therapy regimens: An agile approach in the learning healthcare system toolkit.

OBJECTIVES: Improving the targeted use of drug regimens requires robust real-world evidence (RWE) to address the uncertainties that remain regarding their real-world performance following market entry. However, challenges in the current state of RWE production limit its impact on clinical decisions, as well as its operational scalability and sustainability. We propose an adaptive point-of-care (APoC) platform trial as an approach to RWE production that improves both clinical and operational efficiencies. METHODS AND FINDINGS: We explored design innovations, operational challenges, and infrastructure needs within a multi-stakeholder consortium to evaluate the potential of an APoC platform trial for studying chronic disease treatment regimens using rheumatoid arthritis as a case study. The concept integrates elements from adaptive clinical trials (dynamic treatment regimen strategies) and point-of-care trials (research embedded into routine clinical care) under a perpetual platform infrastructure. The necessary components to implement an APoC platform trial within outpatient settings exist, and present an opportunity for a cross-disciplinary, multi-stakeholder approach. Effective engagement of key stakeholders involved in and impacted by the platform is critical to success. Our collaborative design process identified three high-impact stakeholder-engagement areas: (1) focus on research question(s), (2) design and implementation planning such that it is feasible and fit-for-purpose, and (3) measurement, or meaningful metrics for both clinical (patient outcomes) and system (operational efficiencies) impact. CONCLUSIONS: An APoC platform trial for rheumatoid arthritis integrating innovative design elements in a scalable infrastructure has the potential to reduce important uncertainties about the real-world performance of biomedical innovations and improve clinical decisions.

Improving the efficiency of clinical trials in multiple sclerosis.

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions.

Accelerated annealing of fused filament fabricated (FFF) thermoplastics via an improved core-shell filament.

Thermoplastic parts manufactured via fused filament fabrication (FFF) have limited strength and toughness compared to other types of polymer additive and subtractive manufacturing. Low strength results from poor interlayer adhesion, making FFF parts not suitable for most engineering applications. Post processing solutions, such as annealing, enable healing of these interlayers, thus approaching injection molded parts. Prior work demonstrated a core-shell polycarbonate (PC)-acrylonitrile butadiene styrene (ABS) structured dual material filament to provide thermo-structural stability during annealing of the ABS component; however, annealing was limited to relatively low temperatures (135 °C) and required long annealing times (72 h). In the current work, a PC copolymer with a higher glass transition temperature (173 °C) than conventional PC is processed along with an extrusion-grade ABS into a PC-ABS core-shell filament. This improved dual material filament was printed, annealed, and evaluated via Izod impact testing, ultimately yielding 83% of bulk annealed ABS z-direction strength at an accelerated annealing time (8 h) and higher annealing temperature (155-175 °C). A demonstration part is printed with the dual material filament and annealed at 155 °C for 8 h, resulting in excellent dimensional accuracy, and a ductile failure at 73% higher ultimate load compared to the brittle failure of an as-printed part. This work highlights that material selection and design of a bicomponent filament geometry can lead to parts printed with FFF, with increased strength compared to other post-processing techniques at reduced processing times.

Treatment of primitive myxoid mesenchymal tumour of infancy: a management paradigm focusing on surgical nuances.

Primitive myxoid mesenchymal tumour of infancy (PMMTI) is a rare mesenchymal tumour that typically appears in those under 6 months of age and preferentially affects the deep soft tissues of the trunk and paravertebral spinal regions. PMMTI has only recently been described, and there is scarce literature reporting cases regarding the management paradigm of the tumour. We report the case of an 11-week-old male who presented with bilaterally reduced movement and brisk reflexes in his lower limbs, and irritability. Despite numerous radiological investigations, including MRI, PMMTI was only diagnosed upon biopsy and histopathology. Although PMMTI is known to be relatively unresponsive to chemotherapy, we observed a notable decrease in tumour size after a series of chemotherapy sessions. After two-staged surgical resection of the tumour, the patient is currently stable and under close follow-up. In this article, we aim to report on the patient's clinical presentation, investigations, diagnosis, and treatment, while also discussing the findings from a review of the literature pertaining to future approaches in managing PMMTI. Overall, this case highlights the importance of considering PMMTI in the differential diagnosis of deep soft tissue tumours in young infants and the potential for a combination of chemotherapy and surgical resection to be effective in treating this rare tumour.

Advancement of Nonwoven Fabrics in Personal Protective Equipment.

While nonwoven fabrics have existed for several decades, their usage in personal protective equipment (PPE) has been met with a rapid surge of demands, in part due to the recent COVID-19 pandemic. This review aims to critically examine the current state of nonwoven PPE fabrics by exploring (i) the material constituents and processing steps to produce fibers and bond them, and (ii) how each fabric layer is integrated into a textile, and how the assembled textiles are used as PPE. Firstly, filament fibers are manufactured via dry, wet, and polymer-laid fiber spinning methods. Then the fibers are bonded via chemical, thermal, and mechanical means. Emergent nonwoven processes such as electrospinning and centrifugal spinning to produce unique ultrafine nanofibers are discussed. Nonwoven PPE applications are categorized as filters, medical usage, and protective garments. The role of each nonwoven layer, its role, and textile integration are discussed. Finally, the challenges stemming from the single-use nature of nonwoven PPEs are discussed, especially in the context of growing concerns over sustainability. Then, emerging solutions to address sustainability issues with material and processing innovations are explored.

Management and outcomes of myelomeningocele-associated hydrocephalus in low-income and middle-income countries: a systematic review and meta-analysis protocol.

INTRODUCTION: Hydrocephalus and myelomeningocele (MMC) place disproportionate burdens of disease on low-income and middle-income countries (LMICs). MMC-associated hydrocephalus and its sequelae result in a spectrum of severely devastating clinical manifestations, for which LMICs are disproportionately unprepared in terms of human, capital and technological resources. This study aims to review and compare the management and outcomes of infant MMC-associated hydrocephalus in LMICs and high-income countries. METHODS AND ANALYSIS: This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The following databases will be searched without restrictions on language, publication date or country of origin: EMBASE, MEDLINE, The Cochrane Library, Global Index Medicus, African Journals Online and SciELO. All peer-reviewed studies of primary data reporting management and outcomes of infant MMC-associated hydrocephalus will be included. Where high-quality homogeneous studies exist, meta-analyses will be conducted to compare the management and outcomes of MMC-associated hydrocephalus across socioeconomic and geographical regions of the world. The primary outcome will be treatment failure of the first-line hydrocephalus treatment, which we defined operationally as the performance of a second intervention for the same reason as the first. Secondary outcomes include time to failure, rates of mortality and postoperative complications. ETHICS AND DISSEMINATION: Ethical approval was not applicable because this study does not involve human participants. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at conferences and an interactive web application to facilitate interaction with the findings and promote the discussion and sharing of findings on social media. PROSPERO REGISTRATION NUMBER: CRD42021285850.