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Jing Xian Lee,1 Vina Manjunath,2 S James Talks2 1Faculty of Medicine, Newcastle University, Newcastle upon Tyne, UK; 2Newcastle Eye Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK Background: An increasingly elderly population with a corresponding increase in ophthalmic conditions has led to increased pressure on hospital eye services (HES). In this study, we evaluated the use of a medical retina virtual clinic (MRVC), which has expanded into assessing all new medical retina referrals, where the need for urgent treatment was not clear. Methods: Retrospective analysis of all new patients who were seen in the MRVC between April 2016 and May 2018. Pro forma sheets were used in the MRVC to record the patient history, visual acuity, and type of imaging required. Two consultants reviewed the completed pro formas and images and provided a final diagnosis and management plan. These results and reasons for face-to-face (F2F) clinic appointment requests were analyzed. Results: Six hundred ten new referrals were enrolled in the virtual clinic. The most common diagnosis was diabetic eye disease (59.9%). In the virtual clinic 44.1% were followed up, 28.1% were discharged, and 27.8% were booked an F2F clinic appointment (urgent/routine). The main reason for F2F clinic was to offer treatment. Urgent F2F appointments took place on average 11.9 days after virtual clinic attendance. In only two cases was the image quality felt to be inadequate to assess the retina. Conclusions: MRVC is an effective way of triaging medical retina referrals to allow those patients needing treatment to be seen promptly in the medical retinal service. The use of multimodal ultra-widefield and optical coherence tomography imaging allows assessment of a wide range of retinal pathologies and is a promising solution to alleviate the burden on HES. Keywords: virtual clinic, optical coherence tomography, macular degeneration, choroidal naevus, diabetic retinopathy, teleophthalmology

Premature children with bronchopulmonary dysplasia (BPD) encounter several health issues potentially affecting their health-related quality of life (HRQL). We aimed to determine agreement between children with BPD and their parent's HRQL assessments. Using Patient-Reported Outcomes Measurement Information System (PROMIS) assessment tools, we evaluated agreement and potential bias between parent proxy and child self-reports of the PROMIS-Scale-Global Health-7, the Psychological Stress Experiences Short Form (PSE), and the PROMIS-Profile-25. Fifty-eight child-parent dyads from the Indoor Air Quality and Respiratory Morbidity in Children with BPD study were included. Intraclass correlations (ICC) between child self-report and parent proxy report showed moderate agreement for the Relationships domain (0.44 [95% confidence interval (CI) 0.38-0.53]) and poor agreement for the rest of the Profile-25 dimensions (Mobility, Anxiety, Depression, Pain, and Fatigue; range: 0.05-0.29), Global Health-7 (0.32 [95% CI 0.24-0.48), and PSE (0.34 [95% CI 0.27-0.49]) T-scores. Parents systematically overestimated negative HRQL domains (Pain, Anxiety, or Depression) and underestimated positive domains (Mobility or Relationship). As children age, the child-parent agreement worsens., Conclusions: In school-aged children with BPD, agreement between parents and children on HRQL scales is poor to moderate. Caregivers are biased towards lower HRQL. When possible, HRQL should be assessed in the patient directly., What Is Known: • Children with chronic respiratory diseases often assess their own health related quality of life different than their caregiver would report for the child. • Recent data suggests that parent reported health related quality of life for children with BPD is similar to the normal population., What Is New: • There is a consistent bias for parents to report worse health related quality of life on the Patient Reported Outcomes Measurement Information System (PROMIS) standardized assessment than their school-aged children with BPD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

NPHS1 and NPHS2 are kidney gene components that encode for nephrin and podocin, respectively. They play a role in the progression of congenital (CNS) and steroid-resistant (SRNS) nephrotic syndrome. Hence, this study aimed to determine the prevalence and renal outcomes of NPHS mutations among pediatric patients with CNS and SRNS. We also aimed to identify potential predictors of NPHS mutations in this patient cohort. Overall, this study included 33 studies involving 2123 patients screened for NPHS1, whereas 2889 patients from 40 studies were screened for NPHS2 mutations. The patients' mean age was 4.9 ± 1 years (ranging from birth to 18 years), and 56% of patients were male (n = 1281). Using the random-effects model, the pooled proportion of NPHS1 mutations among pediatric patients with CNS and SRNS was 0.15 (95% CI 0.09; 0.24, p < 0.001, I 2 = 92.0%). The pooled proportion of NPHS2 mutations was slightly lower, at 0.11 (95% CI 0.08; 0.14, p < 0.001, I 2 = 73.8%). Among the 18 studies that reported ESRF, the pooled proportion was 0.47 (95% CI 0.34; 0.61, p < 0.001, I 2 = 75.4%). Our study showed that the NPHS1 (β = 1.16, p = 0.35) and NPHS2 (β = 5.49, p = 0.08) mutations did not predict ESRF in CNS and SRNS pediatric patients. Nevertheless, patients from the European continent who had the NPHS2 mutation had a significantly higher risk of developing ESRF ( p < 0.05, β = 1.3, OR = 7.97, 95% CI 0.30; 2.30) compared to those who had the NPHS1 mutation. We recommend NPHS mutation screening for earlier diagnosis and to avoid unnecessary steroid treatments. More data are needed to better understand the impact of NPHS mutations among pediatric patients with CNS and SRNS.

Widespread North American wildfires in 2023 led to exposure to ambient wildfire smoke outside of traditionally wildfire-prone regions. The objective was to evaluate levels of indoor air pollutants in relation to ambient wildfire smoke exposure in eastern Massachusetts. Using a real-time multipollutant sensor system in five Boston area households, this study assessed indoor fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and total volatile organic compound concentrations (TVOC) two days before and during days of hazardous wildfire smoke exposure (smoke days). The relationship between ambient PM 2.5 from regulatory monitors and indoor PM 2.5 before and during smoke days was investigated by mixed effects linear regression. During smoke days and the preceding non-smoke days, median indoor PM 2.5 was 9.9 µg/m 3 and 3.5 µg/m 3 ( p  < 0.001), respectively; median NO 2 was 20.5 ppb and 18.4 ppb ( p  = 0.11); median TVOC was 6,715 µg/m 3 and 5,361 µg/m 3 ( p  = 0.35). A 1% increase in ambient PM 2.5 was associated with a 0.93% increase in indoor PM 2.5 on smoke days (95% CI, 0.54%-1.32%) and a 0.34% increase on non-smoke days (95% CI, 0.17%-0.66%), though interaction testing of smoke day status was not statistically significant ( p  = 0.14). In Northeastern US homes, indoor PM 2.5 increased significantly during ambient wildfire smoke exposure, which may reflect increased infiltration and increased indoor particle-generating activities during smoke days. Implications : This study reports on household exposure to wildfire smoke in eastern Massachusetts, finding that indoor PM 2.5 more than doubled compared to preceding non-smoke days, while indoor NO 2 and TVOC did not significantly rise. Though the generalizability of this study is limited by the small number of homes studied, the findings suggest that more investigation is needed to understand indoor air pollution during future wildfire smoke exposure in regions not traditionally wildfire-prone and to inform mitigation efforts.

Miniature robots are untethered actuators, which have great prospects to transform targeted drug delivery because they can potentially deliver high concentrations of medicine to the disease site(s) with minimal complications. However, existing miniature robots cannot perform advanced targeted combination therapy; majority of them can at most transport one type of drug, while those that can carry multiple drugs are unable to change their drug-dispensing sequence and dosage. Furthermore, the latter robots cannot transport more than three types of drugs, selectively dispense their drugs, maintain their mobility, or release their drugs at multiple sites. Here, a millimeter-scale soft robot is proposed, which can be actuated by alternating magnetic fields to dispense four types of drugs with reprogrammable drug-dispensing sequence and dosage (dispensing rates: 0.0992-0.231 µL h -1 ). This robot has six degrees-of-freedom motions, and it can deliver its drugs to multiple desired sites by rolling and two-anchor crawling across unstructured environments with negligible drug leakage. Such dexterity is highly desirable and unprecedented for miniature robots with drug-dispensing capabilities. The soft robot therefore has great potential to enable advanced targeted combination therapy, where four types of drugs must be delivered to various disease sites, each with a specific sequence and dosage of drugs., (© 2024 Wiley‐VCH GmbH.)

Introduction: This study compares home-based oscillometry and spirometry for characterizing respiratory system disease in school-aged children with bronchopulmonary dysplasia (BPD) in clinical research. We hypothesized higher rates of successful completion and abnormal cases identified through oscillometry, with correlations between device measurements., Methods: Participants 6-12 years old with BPD in the ongoing Air Quality, Environment and Respiratory Outcomes in BPD (AERO-BPD) study performed oscillometry followed by spirometry at two separate home visits. Parameters measured included airway resistance at 5 Hz(R 5 ), resistance from 5 to 19 Hz(R 5-19 ), resonance frequency(F res ), reactance at 5 Hz(X 5 ), area under the curve between F res and X 5 (AX), forced expiratory volume in 1 second(FEV 1 ), forced vital capacity(FVC), and FEV 1 /FVC. Descriptive statistics identified the proportion of successful tests, correlation in measurements, and rate of lung disease for each device., Results: Among 76 subjects with 120 paired observations, 95% and 71% of participants successfully performed oscillometry and spirometry, respectively, at home visit one. 98% and 77% successfully performed oscillometry and spirometry, respectively, at home visit two. Odds ratios favored oscillometry (range 5.31-10.13, p < 0.01). FEV 1 correlated with AX (correlation coefficient r = -0.27, p = 0.03); FEV 1 /FVC with AX (r = -0.32, p = 0.02); and FEV 1 /FVC with R 5 (r = -0.37, p = 0.01). AX exhibited the highest prevalence of abnormality at 25%; other oscillometry parameters ranged from 5%-22%. Forty-five to sixty-four percent of participants had abnormal spirometry. Oscillometry assessments had significantly lower odds of capturing lung disease (odds ratios 0.07-0.24, p < 0.0001)., Conclusions: School-aged children with BPD demonstrated higher success rates in field-based oscillometry than spirometry. Spirometry exhibited higher rates of abnormality than oscillometry. Moderate correlation exists between device measurements., (© 2024 Wiley Periodicals LLC.)

Background: Epileptic seizures commonly burden low-grade glioma (LGG) patients and negatively impact quality of life, neurocognition, and general patient health. Anti-seizure medications (ASMs) are used to manage seizures but can result in undesired side effects. Our aim was to report our experience in epilepsy in one of the largest case series of LGG patients (reclassified in accordance with the WHO 2021 classification). Furthermore, we evaluate our postoperative seizure frequency difference between LGG patients who use preoperative ASMs and ones with no ASMs., Methods: Data were retrospectively collected from Salford Royal Hospital electronic records and Neuro-Oncology database from 2006 to 2022. Descriptive statistics were performed for demographic analysis, while multivariable analysis was used to determine postoperative seizure-free outcomes., Results: In total, 257 operations were performed on 206 patients. Postoperatively, 114 patients suffered from seizures, and approximately 45.2% of patients developed seizures at 3-12 months postsurgery, with the odds higher in patients on preoperative ASMs. There was no evidence to suggest a higher postoperative seizure rate in patients undergoing awake craniotomy versus general anesthetic. The extent of resection (EOR) was inversely related to seizure failure, with gross-total resection showing a statistically significant reduction in seizures in comparison to all other surgical resections., Conclusions: In our experience, there is no evidence to suggest a reduced postoperative seizure outcome when prescribing preoperative ASMs. EOR is an independent prognosticator for postoperative seizure failure with all other variables demonstrating nonsignificance. Overall, a larger study can investigate the role of ASMs in LGG in greater detail., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis., Methods: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons., Results: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM., Conclusion: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated., (© 2024. Crown.)

We report PEDOT:PSS brushes grafted from gold using surface-initiated atom-transfer radical polymerization (SI-ATRP) which demonstrate significantly enhanced mechanical stability against sonication and electrochemical cycling compared to spin-coated analogues as well as lower impedances than bare gold at frequencies from 0.1 to 10 5 Hz. These results suggest SI-ATRP PEDOT:PSS to be a promising candidate for use in microelectrodes for neural activity recording. Spin-coated, electrodeposited, and drop-cast PEDOT:PSS have already been shown to reduce impedance and improve biocompatibility of microelectrodes, but the lack of strong chemical bonds of the physisorbed polymer film to the metal leads to disintegration under required operational stresses including cyclic mechanical loads, abrasion, and electrochemical cycling. Rather than modifying the metal electrode or introducing cross-linkers or other additives to improve the stability of the polymer film, this work chemically tethers the polymer to the surface, offering a simple, scalable solution for functional bioelectronic interfaces.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Introduction: Since the emergence of COVID-19, we have experienced potent variants and sub-variants of the virus with non-specific neurological manifestations. We observed a surge of the Omicron variant of COVID-19 patients with neurological manifestations where less cases of multisystem inflammatory syndrome in children (MIS-C) were reported. This article describes our experience of children with severe and rare neurological manifestations following COVID-19 infection., Methods: This is a retrospective observational case series of patients under 18 years old who fulfilled the WHO COVID-19 case definition and were referred to our paediatric neurology unit at Hospital Tunku Azizah Kuala Lumpur. Their demographic data, neurological symptoms, laboratory and supporting investigations, neuroimaging, treatment and outcomes were collected and analysed., Results: There were eleven patients with neurological manifestations who fulfilled the WHO COVID-19 case definition. Nine patients presented with seizures and/or encephalopathy, one patient with eye opsoclonus and another patient with persistent limbs myokymia. Based on the history, clinical, electrophysiological and radiological findings, two of them had febrile infection-related epilepsy syndrome, two had acute disseminated encephalomyelitis, two had acute necrotising encephalopathy of childhood, one each had hemiconvulsion-hemiplegia-epilepsy syndrome, acute encephalopathy with bilateral striatal necrosis, hemi-acute encephalopathy with biphasic seizures and reduced diffusion, infection-associated opsoclonus and myokymia., Conclusions: This case series highlighted a wide spectrum of neurological manifestations of COVID-19 infection. Early recognition and prompt investigations are important to provide appropriate interventions. It is essential that these investigations should take place in a timely fashion and COVID-19 quarantine period should not hinder the confirmation of various presenting clinical syndromes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: Higher asthma prevalence and morbidity are seen in inner-city areas, disproportionately affecting low-income families living in substandard housing. Children within these families experience more frequent asthma exacerbations, acute care and emergency department visits, and hospitalizations, thus characterizing severe asthma. In this review, we assess recent published literature focused on indoor and outdoor exposures that contribute to the development and morbidity of asthma., Recent Findings: Many urban environmental exposures contribute to asthma burden, including tobacco/e-cigarette smoke, pest allergens, molds, and possibly synthetic chemicals such as phthalates and bisphenol A, radon, and volatile organic compounds. Individuals living in inner-city areas also experience higher levels of air pollutants and ambient heat, further perpetuating asthma incidence and severity., Summary: This article summarizes the latest advances and provides direction for future research on risk factors, interventions, and public policy to help alleviate the burden of asthma due to urban environment exposures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In this study, we report the implementation of a comprehensive wastewater surveillance testing program at a university campus in Singapore to identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected individuals and the usage of pharmaceuticals and personal care products (PPCPs) as well as other emerging contaminants (ECs). This unique co-monitoring program simultaneously measured SARS-CoV-2 with chemical markers/contaminants as the COVID-19 situation evolved from pandemic to endemic stages, following a nationwide mass vaccination drive. SARS-CoV-2 RNA concentrations in wastewater from campus dormitories were measured using real-time reverse transcription-polymerase chain reaction (RT-qPCR) and corroborated with the number of symptomatic COVID-19 cases confirmed with the antigen rapid test (ART). Consistent results were observed where the concentrations of SARS-CoV-2 RNA detected in wastewater increased proportionately with the number of COVID-19 infected individuals residing on campus. Similarly, a wide range of ECs, including disinfectants and antibiotics, were detected through sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) techniques to establish PPCPs consumption patterns during various stages of the COVID-19 pandemic in Singapore. Statistical correlation of SARS-CoV-2 RNA was observed with few ECs belonging to disinfectants, PCPs and antibiotics. A high concentration of disinfectants and subsequent positive correlation with the number of reported cases on the university campus indicates that disinfectants could serve as a chemical marker during such unprecedented times., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sporadic multiple meningioma are uncommon. Population-based data suggests that these patients have a reduced overall survival when compared to patients with solitary meningioma. The aim of this study was to investigate the clinical outcomes in multiple and solitary meningioma., Methods: A single-center matched cohort study (2008-2018) was performed. Patients with synchronous multiple meningioma at presentation, with no history of prior intracranial radiation, concurrent hormone replacement therapy or features of NF2-schwannomatosis were included. Eligible patients were matched 1:1 to patients with solitary meningioma. Outcomes of interest were occurrence of an intervention, recurrence, new meningioma development and mortality., Results: Thirty-four patients harboring 76 meningioma at presentation were included. Mean age was 59.3 years (SD = 13.5). Thirty-one (91.2%) were female. The median number of meningioma per patient was 2 (range 2-6). Eighteen patients (52.9%) were symptomatic at presentation. Median overall follow-up was 80.6 months (IQR 44.1-99.6). Compared to patients with a sporadic meningioma, there was no difference in intervention rates (67.6% vs 70.6%, P = 0.792). Eight patients (34.8%) with a multiple meningioma had a WHO grade 2 meningioma compared to 7 (29.2%) with a solitary meningioma (P = 0.679). Median recurrence-free survival was 89 months (95% CI 76-104) with no difference between the two groups (P = 0.209). Mean overall survival was 132 months (95% CI 127-138) with no difference between the two groups (P = 0.860). One patient with multiple meningioma developed two further new meningioma 36 months following diagnosis., Conclusion: Sporadic multiple meningioma may not have worse clinical outcomes. Management of patients with sporadic multiple meningioma should be tailored towards the symptomatic meningioma or high-risk asymptomatic meningioma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Analytical thinking safeguards us against believing or spreading fake news. In various forms, this common assumption has been reported, investigated, or implemented in fake news education programs. Some have associated this assumption with the inverse claim, that distractions from analytical thinking may render us vulnerable to believing or spreading fake news. This paper surveys the research done between 2016 and 2022 on psychological factors influencing one's susceptibility to believing or spreading fake news, considers which of the psychological factors are plausible distractors to one's exercise of analytical thinking, and discusses some implications of considering them as distractors to analytical thinking. From these, the paper draws five conclusions: (1) It is not analytical thinking per se, but analytical thinking directed to evaluating the truth that safeguards us from believing or spreading fake news. (2) While psychological factors can distract us from exercising analytical thinking and they can also distract us in exercising analytical thinking. (3) Whether a psychological factor functions as a distractor from analytical thinking or in analytical thinking may depend on contextual factors. (4) Measurements of analytical thinking may not indicate vulnerability to believing or spreading fake news. (5) The relevance of motivated reasoning to our tendency to believe fake news should not yet be dismissed. These findings may be useful to guide future research in the intersection of analytical thinking and susceptibility to believing or spreading fake news., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Objective: This study was undertaken to determine the hemoglobin A1c (HbA1c) and modified glucose-ketone index (mGKI) in children on different types of ketogenic diet (KD) for treatment of drug-resistant epilepsy, with attempts to evaluate their relationships with components of diet regime and other biomarkers., Methods: We conducted a cross-sectional study in children with drug resistant epilepsy aged between 6 months and 18 years, who were on various types of KD therapies without any change in regime for at least 3 months. Parental interview, review of medical records, and a single measurement for blood ketone, HbA1c, and plasma carnitine were performed. mGKI was the ratio of an average plasma glucose estimated from HbA1c to blood β-hydroxybutyrate level., Results: Thirty-four patients were recruited with a median blood ketone of 2.90 mmol·L -1 and median HbA1c of 4.55%. Those on classical KD (cKD) had higher blood ketone (p = .031) and lower HbA1c (p = .010) and mGKI (p = .021) than those receiving modified Atkins diet, although both shared similar percentages of calories from carbohydrate (p = .211). The cKD and medium-chain triglyceride (MCT) KD groups had similar HbA1c (p = .252) and mGKI (p = .510). Blood ketone (p = .045) and the percentage of calories from MCT (p = .037) were the two main independent variables, inversely correlating with HbA1c. Other than plasma acylcarnitine (p = .047), neither blood ketone (p = .188) nor HbA1c (p = .170) could predict seizure reduction reliably. Both plasma acylcarnitine ≥ 6 μmol·L -1 (p = .013) and mGKI ≤ 2.2 (p = .013) were significantly associated with good seizure control., Significance: HbA1c could potentially be useful for monitoring KD adherence or, indirectly, systemic ketosis in nondiabetic children on KD for drug-resistant epilepsy. Plasma acylcarnitine and mGKI could be important biomarkers in the management of KD therapy., (© 2022 International League Against Epilepsy.)

Patients with sickle cell disease (SCD) are at higher risk of getting severe COVID-19 infection. This systematic review and meta-analysis aimed to determine the role of serum ferritin in predicting ICU admission and mortality among patients with SCD following COVID-19 infection. A systematic search was conducted in PubMed, Scopus, Web of Science, Embase, WHO COVID-19 database, ProQuest, and Cochrane Library for articles published between 1st December 2019 to 31st November 2021. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Eleven articles (7 cohorts and 4 case series) were included in this review. Pooled mean serum ferritin level on admission was 1581.62 ng/mL while pooled proportion of ICU admission and mortality were 0.10 (95% CI 0.06; 0.16, prediction interval 0.04; 0.23, p = 0.29, I 2 = 17%) and 0.07 (95% CI 0.05; 0.11, prediction interval 0.04; 0.12, p = 0.68, I 2 = 0%) respectively. Meta-regression showed that serum ferritin did not predict for both ICU admission (regression coefficient = 0.0001, p = 0.3523) and mortality (regression coefficient = 0.0001, p = 0.4029). Our analyses showed that serum ferritin may not be a useful marker to predict the outcomes of COVID-19 infection among patients with SCD. More data are required to identify a reliable tool to identify patients with SCD who are at risk of getting severe COVID-19 infection., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=287792, PROSPERO Registration: CRD42021287792., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Chieng, Abdul Jalal, Tan and Lau.)

Oxidative stress-related conditions associated with lung cells, specifically lung cancer, often lead to a poor prognosis. We hypothesized that platinum nanoparticles (PtNPs) can play a role in reversing oxidative stress in human lung adenocarcinoma A549 epithelial lung cell lines. Hydrogen peroxide (H 2 O 2 ) was used to induce oxidative stress in cells, and the ability of PtNPs to lower the oxidative stress in the H 2 O 2 treated epithelial lung cell line was determined. The differential capacity of PtNPs to remove H 2 O 2 was studied through cell viability, nanoparticle uptake, DNA damage, ROS production, and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Results indicated that a higher concentration of PtNPs exhibited a higher antioxidant capacity and was able to reduce DNA damage and quench ROS production in the presence of 350 µM H 2 O 2 . All antioxidant enzymes' activities also increased in the PtNPs treatment. Our data suggested that PtNPs could be a promising antioxidant in the treatment of lung cancer.

Introduction: A widely used guide of 2 mm incisal show at rest is used as an esthetic guide in treatment planning for many patients. However, this does not consider the lip form at rest. This study aimed to investigate the most esthetic incisal show at rest, at varying lip forms, perceived by dental professionals and laypeople., Methods: Three volunteers of each gender and type of lip form (straight, moderate, and high) were recruited. For each volunteer, 6 images of their perioral region with a variable incisal display at rest were generated. A survey was conducted whereby respondents were asked to grade the attractiveness of each image using a numerical visual analog scale from 0-10., Results: A survey sample of 107 respondents participated in the study (male-to-female ratio = 37 to 70; dental professionals-to-laypeople ratio = 50 to 57). Mann-Whitney U-test was used to analyze the differences in preferences between the various groups (P <0.05). Both dental professionals and laypeople responded that 2 mm incisal show at rest is only suitable for patients with straight lip form. However, for patients with moderate or high lip forms, an incisal show of 4-5 mm was preferred. There was also no significant difference between the perceived ideal incisal show of dental professionals and laypeople, except for the ideal incisal show of models with straight lip form., Conclusions: The guide of 2 mm incisal show at rest is appropriate only for patients with straight lip form. Patients with moderate or high lip form should have a greater incisal show. This finding was agreed on by both dental professionals and laypeople, regardless of their gender., (Copyright © 2022. Published by Elsevier Inc.)

CsPbBr 3 quantum dots (QDs) have recently gained much interest due to their excellent optical and scintillation properties and their potential for X-ray imaging applications. In this study, we blended CsPbBr 3 QDs with resin at different QD concentrations to achieve thick films and to protect the CsPbBr 3 QDs from environmental moisture. Then, their scintillation properties are investigated and compared to the traditional commercial scintillators, CsI:Tl microcolumns, and Gadox layers. The CsPbBr 3 QD-resin sheets show a high light yield of up to 21 500 photons/MeV at room temperature and a relatively small variation in light yield across a wide temperature range. In addition, the CsPbBr 3 QD-resin sheets feature a small scintillation afterglow. The CsPbBr 3 QD-resin sheets show a negligible trap density for the concentration below 50% weight, indicating that traps might arise from the aggregation of the QDs. The CsPbBr 3 QD-resin sheets are also very stable at low irradiation intensities and relatively stable at higher intensities, with higher CsPbBr 3 QD concentrations being more stable. Gamma-ray-excited-time-resolved emission measurements at 662 keV showed that the CsPbBr 3 QD-resin sheets have an average scintillation decay time between 108 and 176 ns, which are still 10 000 and 6000 times faster than CsI:Tl and Gadox, respectively. Imaging tests show that the CsPbBr 3 QD-resin sheets have a mean transfer function of 50% at 2 lp/mm and 20% at 4 lp/mm, comparable to that of commercial Gadox layers. This feature makes CsPbBr 3 QD-resin sheets a good candidate for the low-cost, flexible X-ray imaging screens and γ-ray applications.

Purpose: This systematic review aimed to synthesize the effectiveness of psychosocial interventions on caregivers of advanced cancer patients, in comparison with usual care, on caregivers' quality of life (QoL), anxiety, and depression symptoms., Methods: Comprehensive searches for published and unpublished studies were performed using nine electronic databases, two trial registers, and reference lists of included studies. Two reviewers independently screened, appraised, and extracted data. The Cochrane risk of bias tool was used to appraise the methodological quality of included studies, while the Cochrane data extraction tool was used to elicit relevant information. Meta-analysis, narrative analysis, and sensitivity analysis were conducted to synthesize data. Standardized mean differences (SMD) represented effects of psychosocial interventions., Results: Fifteen randomized controlled trials were included in this review. At post-intervention, findings revealed a significant small pooled effect size (SMD = 0.45) on QoL and significant moderate effect on depression (SMD = - 0.65). However, a small non-significant pooled effect size was observed on anxiety (SMD = - 0.24). At follow-up assessments, effect sizes of all outcomes were small and non-significant. Overall quality of evidence was rated very low for all outcomes and most studies had unclear or high risk of bias. Thus, results should be interpreted with caution., Conclusion: Psychosocial interventions were effective in improving QoL and depression among caregivers of persons with advanced cancer. However, future randomized control trials with lower risk of bias, larger sample size, detailed participant characteristics, and informative interventions are desirable., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This systematic review aimed to provide an overview of the clinical profile and outcome of COVID-19 infection in patients with hemoglobinopathy. The rate of COVID-19 mortality and its predictors were also identified. A systematic search was conducted in accordance with PRISMA guidelines in five electronic databases (PubMed, Scopus, Web of Science, Embase, WHO COVID-19 database) for articles published between 1st December 2019 to 31st October 2020. All articles with laboratory-confirmed COVID-19 cases with underlying hemoglobinopathy were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Thirty-one articles with data on 246 patients with hemoglobinopathy were included in this review. In general, clinical manifestations of COVID-19 infection among patients with hemoglobinopathy were similar to the general population. Vaso-occlusive crisis occurred in 55.6% of sickle cell disease patients with COVID-19 infection. Mortality from COVID-19 infection among patients with hemoglobinopathy was 6.9%. After adjusting for age, gender, types of hemoglobinopathy and oxygen supplementation, respiratory (adj OR = 89.63, 95% CI 2.514-3195.537, p = 0.014) and cardiovascular (adj OR = 35.20, 95% CI 1.291-959.526, p = 0.035) comorbidities were significant predictors of mortality. Patients with hemoglobinopathy had a higher mortality rate from COVID-19 infection compared to the general population. Those with coexisting cardiovascular or respiratory comorbidities require closer monitoring during the course of illness. More data are needed to allow a better understanding on the clinical impact of COVID-19 infections among patients with hemoglobinopathy. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42020218200., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Chieng, Lau and Tan.)

Background: Exposure to neurosciences, especially neurosurgery, in UK medical schools is limited and variable. This combined with the fact that neurology and neurosurgery have been perceived as notoriously difficult subjects could negatively affect confidence and efficiency in junior doctors when assessing and managing patients with neurosurgical conditions. This study aims to assess the impact of a neurosurgery virtual lecture series on foundation doctors' and medical students' confidence and knowledge in the assessment and management of neurosurgical patients., Methods: Six virtual lectures were delivered via Zoom weekly between October and November 2020 covering lesion localisation, neuroradiology, neurosurgical emergencies, trauma assessment, and neuro-ICU. Data was collected relating to participants' pre- and post-lecture self-perceived confidence levels and performance of five SBA questions, lecture series satisfaction, and feedback., Results: 31 participants in a district general hospital attended the virtual lecture series (17 foundation doctors and 14 medical students). Pre-lecture, foundation doctors felt significantly more confident than medical students in trauma assessment, spinal emergencies and neurointensive care medicine. In all lectures, participants' median confidence levels improved significantly post-lecture (p < 0.05). There was no significant difference in the performance of pre-lecture SBA questions between foundation doctors and medical students in all but one lecture, which was the neuro-ICU lecture where foundation doctors scored better (3.0 vs 1.0, p = 0.012). In both cohorts, the participants' median scores in SBA questions (objective marker of knowledge improvement) increased significantly post-lecture in all lectures., Conclusion: This study has shown that this neurosurgery virtual lecture series that was focused and low-cost was well received, improved knowledge and confidence of junior doctors and medical students in assessing and managing neurosurgical patients. Future expansion of this lecture series into regional or national initiative can further increase exposure to neurosurgery, ultimately improving the care of neurosurgical patients., Competing Interests: None., (© 2021 The Authors.)

Takotsubo cardiomyopathy (TCM) is characterized by temporary wall motion abnormality of the left ventricle. There is much debate upon the prognostic parameters. We conducted a systematic review and meta-analysis to investigate whether LVEF and the presence of apical ballooning predict long-term mortality in TCM. PubMed and Embase were searched through to October 30, 2017 without language restrictions, followed by an additional search through to February 2, 2020. Our search identified 18 studies that met the inclusion criteria, with a total of 5168 patients. Reduced LVEF as a categorical variable was associated with more than threefold increase in mortality risk in TCM patients (HR 3.10; 95% CI 1.78-5.42; P < 0.0001; I 2  = 57%). Further subset analyses with the exclusion of studies consisting of patients with coronary artery disease revealed another significant relationship between LVEF and mortality (HR 3.13; 95% CI 1.392-7.031; P < 0.006; I 2  = 58%). LVEF as a continuous variable was also found to be associated with increased mortality risk. However, this relationship only retained significance when computing odds ratios instead of hazard ratios (OR 0.95; 95% CI 0.93-0.98; P < 0.001; I 2  = 0%). Finally, the existence of apical ballooning failed to demonstrate any link with an increased risk of mortality (HR 1.26; 95% CI 0.97-1.64; P = 0.09; I 2  = 34%). LVEF and apical ballooning are both potential prognostic markers for mortality.

Purpose . Work performance is closely related to one's attention level. In this study, a brain-computer interface (BCI) device suitable for office usage was chosen to quantify the individual's attention levels. Methods . A BCI system was adopted to interface brainwave signals to a coffee maker via three ascending levels of laser detectors. The preliminary test with this prototype was to characterize the attention level through the collected coffee amount. Here, the preliminary testing was comparing the correlation between the attention level and the participants' cumulative grade point average (CGPA) and scores from the 21-item depression, anxiety, and stress scale (DASS-21) and the attentional control scale (ACS) using ordinal regression. It was assumed that a greater CGPA would generate a greater attention level. Result . The generated coffee amount from the BCI system had a significant positive correlation with the CGPA ( p  = 0.004), mild depression ( p  = 0.019) and mild and extremely severe anxiety ( p  = 0.044 and p  = 0.019, respectively) and a negative correlation with the ACS score ( p  = 0.042). Conclusion . This simple and cost-effective prototype has the potential to enable everyone to know their immediate attention level and predict the possible correlation to their mental state.

Introduction: The COVID-19 pandemic has led to changes in NHS surgical service provision, including reduced elective surgical and endoscopic activity, with only essential emergency surgery being undertaken. This, combined with the government-imposed lockdown, may have impacted on patient attendance, severity of surgical disease, and outcomes. The aim of this study was to investigate a possible 'lockdown' effect on the volume and severity of surgical admissions and their outcomes., Methods: Two separate cohorts of adult emergency general surgery inpatient admissions 30 days immediately before (February 16, 2020 to March 15, 2020), and after UK government advice (March 16, 2020 to April 15, 2020). Data were collected relating to patient characteristics, severity of disease, clinical outcomes, and compared between these groups., Results: Following lockdown, a significant reduction in median daily admissions from 7 to 3 per day (p < 0.001) was observed. Post-lockdown patients were significantly older, frailer with higher inflammatory indices and rates of acute kidney injury, and also were significantly more likely to present with gastrointestinal cancer, obstruction, and perforation. Patients had significantly higher rates of Clavien-Dindo Grade ≥3 complications (p = 0.001), all cause 30-day mortality (8.5% vs. 2.9%, p = 0.028), but no significant difference was observed in operative 30-day mortality., Conclusion: There appears to be a "lockdown" effect on general surgical admissions with a profound impact; fewer surgical admissions, more acutely unwell surgical patients, and an increase in all cause 30-day mortality. Patients should be advised to present promptly with gastrointestinal symptoms, and this should be reinforced for future lockdowns during the pandemic., Competing Interests: Declaration of competing interest Nil., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: The importance of Oct4 and Sox2 in maintaining pluripotency and self-renewal is well-understood, but the functions of Klf4 and c-Myc has not been fully investigated. In the present study, we attempted to determine the roles of Klf4 and c-Myc on pluripotency maintenance of porcine induced pluripotent stem (piPS) cells., Materials and Methods: In this experimental study, we performed short hairpin RNA (shRNA) to knock down the Klf4 and c-Myc functions of piPS cells and examined pluripotency markers and teratoma formation to evaluate piPS cell pluripotency. The shRNA-Klf4 and shRNA-c-Myc vectors containing a reporter gene, TagFP635, were transfected into piPS cells by lentivirus infection. The piPS cells fully expressing infrared fluorescence were selected to confirm gene knockdown of Klf4 and c-Myc reverse transcription-polymerase chain reaction (RT-PCR). Next, for pluripotency evaluation, expression of pluripotency markers was detected by immunocytochemical staining, and capability of teratoma formation was investigated by piPS cell transplantation into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice., Results: Our findings indicated that Klf4 and c-Myc functions of piPS cells were knocked down by shRNA transfection, and knockdown of Klf4 and c-Myc functions impaired expression of pluripotency markers such as Oct4, AP, SSEA-3, SSEA-4, TRA-1-6, and TRA-1-81. Furthermore, piPS cells without Klf4 and c-Myc expression failed to form teratomas., Conclusions: The pluripotency of piPS cells are crucially dependent upon Klf4 and c-Myc expression. These findings, suggesting potential mechanisms of Klf4 and c-Myc contribution to piPS cell formation, have important implications for application, regulation, and tumorigenesis of piPS cells., Competing Interests: The authors declare no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

The PI3K/mTOR/AKT pathway is an integral regulator of survival and drug resistance in multiple myeloma (MM). VS-5584 was synthesized with dual-specific and equipotent activity against mTORC1/2 and all four Class I PI3K isoforms so as to durably inhibit this pathway. We show that VS-5584 is highly efficacious against MM cell lines even in the presence of IL-6 and IGF-1 and that this growth inhibition is partially dependent on Bim. Importantly, VS-5584 triggers apoptosis in patient cells with a favorable therapeutic index. Gene expression profiling revealed a VS-5584-induced upregulation of RARRES3, a class II tumor suppressor gene. MM patient databases, UAMS and APEX, show that RARRES3 is under-expressed in 11q13 subsets which correlates with the reduced effectiveness of VS-5584 in 11q13 cell lines. Silencing RARRES3 expression significantly rescues VS-5584-induced cell death and increases cyclin D2 expression but not cyclin D1 or other cyclins implying a role for RARRES3 in cell cycle arrest. In vivo, VS-5584 significantly reduces the tumor burden of MM mouse xenografts. We further identified that VS-5584 synergised with Dexamethasone, Velcade, and exceptionally so with HDAC inhibitor, Panobinostat. Interestingly, this was consistently observed in several patient samples, proposing a promising novel clinical strategy for combination treatment especially in relapsed/refractory patients., Competing Interests: CONFLICTS OF INTEREST Stefan Hart was an ex-employee of S*Bio. The authors declare no competing financial interests.

Silver nanostructures have expansive applications in catalysis, photonic and electronic devices. In this work, nanostructured silver micro-colloids (MCs) with uniform in size and shape (size distribution <5%) were synthesized via rapid reduction of silver nitrate by ascorbic acid with controlled agglomeration and coalescence. We further propose that the formation of silver MCs was controlled by the chemical reaction kinetics which is governed by the concentration of reduced silver, Agº formed in solution. Preliminary electrical measurements of the highly conductive silver MCs demonstrated their potential application as inks for printed electronics.

A 384-well-based antibacterial assay amenable for high-throughput screening and combination testing is described. The assay uses 100-500nL of test compounds and tolerates up to 2.5% dimethyl sulfoxide concentrations. It can be used for screening compound libraries and testing combinatory/synergistic/antagonistic effects of antibiotics, small molecules, and natural product extracts., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Genomic deletion at tumor suppressor loci is a common genetic aberration in human cancers. The study aimed to explore candidate tumor suppressor genes at chromosome 4q25-q28.2 and to delineate novel prognostic biomarkers associated with colorectal cancer (CRC)., Methods: Deletion mapping of chromosome 4q25-q28.2 was conducted in 114 sporadic CRC by loss of heterozygosity study with 11 microsatellite markers. A novel candidate tumor suppressor gene, namely NDST4, was identified at 4q26. Gene expression of NDST4 was investigated in 52 pairs of primary CRC tissues by quantitative reverse transcription-polymerase chain reaction. Allelic loss of NDST4 gene was further determined in 174 colorectal carcinomas by loss of heterozygosity analysis, and then was assessed for clinical relevance., Results: One minimal deletion region was delineated between D4S2297 and D4S2303 loci at 4q26, where NDST4 was the only gene that had markedly been downregulated in CRC tumors. By laser capture microdissection, NDST4 RNA expression was demonstrated in colonic epithelial cells, but was undetectable in tumor cells. In total, 30 (57.7%) of 52 colorectal carcinomas showed a dramatic reduction in NDST4 gene expression compared with matched normal mucosae. The genetic loss of NDST4 was significantly associated with advanced pathological stage (P = 0.039) and poorer overall survival of patients (P = 0.036)., Conclusions: NDST4 gene is a novel candidate tumor suppressor gene in human cancer, and the loss of its function might be involved in CRC progression. In addition, the loss of heterozygosity assay, which was established to determine the allelic loss of NDST4 gene, could be a cost-effective tool for providing a useful biomarker of adverse prognosis in CRC.

Interactions between Transcription Factors (TFs) are necessary for deciphering the complex mechanisms of transcription regulation in eukaryotes. We proposed a novel HV-kernel based SVM classifier to classify TF-TF pairs based on their protein domains and GO annotations. Two types of pairwise kernels, namely, a horizontal kernel and a vertical kernel, were combined to evaluate the similarity between a pair of TFs, and a Genetic Algorithm was used to obtain kernel and feature weights to optimise the classifier's performance. We showed that our proposed HV-SVM method can make accurate predictions of TF-TF interactions even in the higher and more complex eukaryotes.

We hypothesised that T(reg) cells preferentially expand/infiltrate inside murine mesotheliomas. Immunotherapy based on the manipulation of T(reg) cell populations should therefore be targeted to the tumour site. The AE17 murine mesothelioma model was used for this study. Both intra-tumoural T(reg) cells and those in the periphery of tumour-bearing mice were identified by flow cytometry. The effect on tumour growth of intra-tumoural depletion of T(reg) cells using the PC61 anti-CD25 mAb was then examined. We identified CD4+ T(reg) cells co-expressing both the CD25 cell surface marker and the transcription factor Foxp3 within murine mesotheliomas. These intra-tumoural T(reg) cells increase significantly as a percentage of total CD4+ T cells within the tumour as it grows. We showed that the depletion of intra-tumoural T(reg) cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of T(reg) cells is a new, clinically relevant treatment option for established tumours.