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In this review, we describe evidence that supports building a metaverse to promote healthy longevity. We propose that the metaverse offers several physical advantages (architecture, music, and nature), social (accessibility, affordability, community-building, and relief of social anxiety), and therapeutic (immersive, anti-inflammatory, and adjunctive use in complementary and integrative medicine). Lifelogging by patients may help clinicians personalize interventions by matching data to therapeutic outcomes. Although the metaverse cannot entirely replace our current model of care, a strategic approach will ensure adequate resource allocation and value assessment. In a collaborative effort between Reulay, Inc and Mayo Clinic, we are building a platform for the delivery of personalized and idiographic interventions to promote healthy longevity. To this end, we are using specific science-informed art design to reduce stress and anxiety for patients, with the progressive addition of integrated care elements that connect to this framework and connect treatment response to biomarkers that are relevant to healthy longevity. This review is a commentary on the thought process behind this effort.

This work assessed the effects of frequency & the pulse duration ratios on the weldability & structure-property relationships for the magnesium alloy AZ31B. In addition, AC/DC pulse welding with different pulse duration ratios was explored, to assess controlled repair welding on magnesium alloy castings. Complete penetration welds can be produced with conventional GTA welding using a heat input of ∼500 J/mm without the need for an active flux. However, the weld metal has a coarse grain structure and micro cracks, suggesting the need for an even better control of heat input for achieving defect free welds. Pulse GTA welding with at lower frequencies give relatively deeper penetration joints at different pulse duration ratios (1:1, 1:2 and 1:4). However, the full penetration welds are possible only with pulse duration ratio of 1:1. All the welds produced under pulsed GTA welding conditions were defect free. The grain sizes of the weld metals were much finer than for conventional GTA welding conditions and have a higher hardness compared to conventional GTA weld & also the parent alloy. Use of AC/DC mix for pulse welding, with the peak current being AC and the base current as DC, yields shallow penetration welds with no defects. The resultant weld metal microstructures are of finer grain size, and with finely distributed β-phase particles. This welding technique can be exploited for repair welding of magnesium alloy castings that have near-surface defects.

Background: In the NPCDCS program of Government of India, capacity building of health professionals on palliative care is a key component in rehabilitaion of cancer and other NCDs. However as palliative care teaching is still not mandatory in undergraduate medical curriculum, a medical graduate lacks knowledge and confidence in providing palliative care. Understanding the existing levelof knowledge and perceptions of students towards palliative care can facilitate planning a need-based curriculum. Aim: To assess the knowledge and perceptions in palliative care among undergraduate medical students in Puducherry, South India. Methods: After ethical clearance, a semi structured questionnaire comprising 15 knowledge questions and seven perception statements on palliative care was administered to 265 pre-final and final year medical students. The data were analyzed using SPSS-23. Results: Cancer (88.6%), AIDS (28.6%), Spinal trauma (11.6%), XDR TB (5.6%) and Coma (4.5%) were mentioned as diseases that need palliative care. Improving quality of life (46.4%) and relief of pain (30.5%) were mentioned as the purposes of palliative care. Only 15.8% said palliative care starts from the time of diagnosis. About 54.7% students were unaware of main drugs in Step I & II in WHO Pain Ladder. Majority (90.2%) felt oral morphine relieves cancer pain and 47.5% felt it causes addiction. Nearly half of students (48.6%) felt that patients can be reassured during communication. Majority (83.4%) favored inclusion of palliative care teaching in undergraduate curriculum. Conclusion: The findings indicate the need for filling the knowledge gap by focussed training of undergraduate students in palliative care.

Background: Hypotension, which is a common adverse effect of induction of anesthesia, may be especially detrimental in neurosurgical patients. Hence, it is important to investigate hemodynamic parameters which may be useful in identifying patients at risk of hypotension, following induction. Our study was designed to assess the utility of parameters derived from ultrasonography, pulse oximeter and arterial line for predicting post-induction hypotension. Methods: The study was designed as a prospective, observational trial. Written informed consent was obtained from 100 American Society of Anesthesiologists (ASA) 1 and 2 patients, between 18-60 years of age, scheduled for elective craniotomy for brain tumors. Arterial cannula was inserted before induction of anesthesia and connected to Vigileo cardiac output monitor. Baseline stroke volume variation (SVV), stroke volume (SV), cardiac index (Ci), cardiac output (CO) and pulse pressure variation (PPV) were recorded. Plethysmography variability index (PVI) and perfusion index (PI) were obtained from the Masimo rainbow SET® Radical-7® pulse oximeter. Ultrasonographic assessment of the inferior vena cava (IVC) was performed before induction of anesthesia and again within 15 min after induction. Maximum and minimum IVC diameters (dIVCmax and dIVCmin) and collapsibility index (CI) were measured. All the other aforementioned parameters were recorded every minute starting at induction, until the 15th minute following induction. Results: PI, CI and dIVCmax were found to have the largest AUCROC for the prediction of post-induction hypotension (AUCROC 0.852, 0.823 and 0.781 respectively). Multiple logistic regression analysis revealed CI to be the most significant independent factor for the prediction of post-induction hypotension. Conclusion: Non-invasively derived hemodynamic parameters like dIVCmax, CI and PI were more accurate for the prediction of post-induction hypotension, compared to invasively derived parameters.

Laser Additive Manufacturing (LAM) is a promising technology for manufacturing gas turbine components with enhanced design capability and a significant reduction in part weight. Additive manufacturing of alloy 718 using Laser Powder Bed fusion (L-PBF) process poses certain challenges pertaining to complex residual stress, micro-segregation of Nb, and undesired Laves phase formation in the as-printed state. The built-up residual stress and undesired brittle phase may lead to cracks and build failures. This article studied residual stress evolution during L-PBF of alloy 718 using Finite Element (FE) thermo-mechanical simulation implemented in Simufact Additive® software. The model adopted the bundling of physical powder in voxel mesh to minimize the computational time and mimic the actual process scenario during part-scale simulation. Experimental flow curves generated from Gleeble 3800® tests at elevated temperatures were utilized to calibrate material property for better accuracy in the FE simulation. The calibrated model was used to study the residual stress evolution during support structure removal. Verification and validation of simulated results were performed using X-ray diffraction (XRD) measurements. The simulated value agrees well with the experimental value with a maximum deviation of 7%. Finally, the experimentally validated model was used to correlate the effect of layer thickness variation on residual stress evolution.

Corona virus disease-19 (COVID-19) vaccines have been approved for emergency use. Ocular adverse effects following the vaccines have been reported. Purpose: To report an unique case of recurrent central serous chorioretinopathy following both doses of COVID-19 vaccine. Observations: A 40-year-old male presented with blurring of vision in the left eye during 2 days following COVISHIELD™ (Serum Institute of India). He had a previous history of central serous chorioretinopathy in the right eye 2 years back and was treated with micropulse laser. Ocular examination showed a best corrected visual acuity of 20/20 right eye and 20/60 left eye. Fundus evaluation of left eye showed central serous chorioretinopathy. Spectral domain optical coherence tomography of the left eye revealed neurosensory detachment. Fundus fluorescein angiography of the left eye showed multiple window defects and ink-blot appearance in the macula. Oral eplerenone 50mg once a day for a month showed significant reduction in the subretinal fluid. Patient developed central serous chorioretinopathy in the left eye 3 days after 2nd dose of COVISHIELD™. Conclusion and Importance: CSCR following vaccination may be a temporal event. In our patient it occurred following the vaccination. This is the first case of a recurrent CSCR after either dose of COVID-19 vaccination. Ocular symptoms after vaccination warrant a thorough eye evaluation.

Purpose: Dengue fever (DF) epidemics in Singapore in 2005–2006 and 2007 were caused predominantly by dengue virus serotypes 1 (DENV-1) and 2 (DENV-2) respectively. We investigated the prevalence of ophthalmic manifestations during these consecutive epidemics. Methods: Seropositive DF patients admitted to the hospital during two separate dengue epidemics were enrolled from June 2005 to December 2007. Demographic, ophthalmic, and laboratory data were collected. The primary outcome measures were differences in ophthalmic and laboratory features across the two epidemics. Factors associated with increased risk of developing various DF-related ophthalmic manifestations were the secondary outcome measures. Results: Of the 115 patients enrolled, 109 (94.7%; 33 in 2005–2006 and 76 in 2007) completed the eye screening protocol. Majority of patients were Chinese (65, 59.6%) and males (81, 74.3%). The mean age was 40.8 years (range, 18–87). Colour vision impairment (12 vs 14 [36.4% vs 18.7%]; P ​= ​0.04), cotton wool spots (10 vs 3 [30.3% vs 3.9%]; P ​

Early chest compressions and rapid defibrillation are important components of cardiopulmonary resuscitation (CPR). American heart association (AHA) recommends two breaths to be delivered for every 30 compressions for an adult cardiac arrest victim. Patient with an advanced airway like endotracheal tube (ETT) should be given one breath every 6 s without interruptions in chest compression (10 breaths per minute). All of the modern mechanical ventilators have option to generate spontaneous breaths by the patient if the patient has spontaneous respiratory efforts. During CPR, the mechanical ventilator is fallaciously sensing the chest compressions as patient's spontaneous trigger and thereby it delivers higher respiratory rates. Avoiding excessive ventilation is one of the components of high quality CPR as excessive ventilation decreases venous return thereby decreasing the cardiac output and also it affects intra-thoracic pressure thereby adversely affects intra-arterial pressure. As modern ventilators have trigger for spontaneous breaths and they will be erroneously triggered by chest compressions, it would be prudent to use volume marked resuscitation bags or manual breathing devices (manual self-inflating resuscitation bag, Bain's circuit) for delivering breaths which can be synchronised with compression phase of CPR at RR of 10 breaths per min with advanced airway in place. If any patient who is on mechanical ventilation develops cardiac arrest, patient should be disconnected from the mechanical ventilator and should be ventilated manually. Manual ventilation with aforementioned breathing devices should be used in a patient without and with advanced airway devices during CPR.

Paget's disease of bone (PDB) is a chronic localized bone disorder in an elderly population. Environmental factors such as paramyxovirus are implicated in PDB and measles virus nucleocapsid protein (MVNP) has been shown to induce pagetic osteoclasts (OCLs). However, the molecular mechanisms underlying MVNP stimulation of OCL differentiation in the PDB are unclear. We therefore determined the MVNP regulated gene expression profiling during OCL differentiation. Agilent microarray analysis of gene expression identified high levels of SIRPβ1 (353-fold) expression in MVNP transduced human bone marrow mononuclear cells stimulated with RANKL. Real-time PCR analysis further confirmed that MVNP alone upregulates SIRPβ1 mRNA expression in these cells. Also, bone marrow mononuclear cells derived from patients with PDB showed high levels of SIRPβ1 mRNA expression compared to normal subjects. We further show that MVNP increases SIRPβ1 interaction with DAP12 adaptor protein in the presence and absence of RANKL stimulation. shRNA knockdown of SIRPβ1 expression in normal human bone marrow monocytes decreased the levels of MVNP enhanced p-Syk and c-Fos expression. In addition, SIRPβ1 knockdown significantly decreased MVNP stimulated dendritic cell–specific transmembrane protein (DC-STAMP) and connective tissue growth factor (CTGF) mRNA expression during OCL differentiation. Furthermore, we demonstrated the contribution of SIRPβ1 in MVNP induced OCL formation and bone resorption. Thus, our results suggest that MVNP modulation of SIRPβ1 provides new insights into the molecular mechanisms which control high bone turnover in PDB.

Summary: The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1−/− mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation. : NLRP3 inflammasome activation contributes to chronic inflammation associated with autoinflammatory disease, yet understanding of NLRP3 inflammasome regulation is incomplete. Hughes et al. show that the deglutathionylating enzyme GSTO1-1 promotes NLRP3 inflammasome activation through deglutathionylation of NEK7. Furthermore, the GSTO1-1 inhibitor C1-27 reduces NLRP3 inflammasome activation in vitro and in vivo. Keywords: NLRP3 inflammasome, GSTO1-1, glutathione, NEK7, IL-1β, deglutathionylation, pyroptosis

The corrosion behaviour of Mg–6Al–1Zn + XCe (where X = 0.5, 1.0, 1.5 and 2.0 wt% Ce) alloys, aged for 18 h at different temperatures of 180 °C, 200 °C, 220 °C and 240 °C, was studied in 3.5 wt% NaCl solution. The salt spray test was conducted in accordance with ASTM-B117 standard (fog test). The corrosion morphologies, corrosion rate and the composition of the corrosion products were investigated by X-ray Diffraction (XRD), Optical Microscopy (OM) and Scanning Electron Microscopy (SEM) techniques. The results show the cerium addition and ageing treatment has significantly influenced the corrosion morphologies and the corrosion rate. In AZ61 alloy, the intermetallic β (Mg17Al12) phase acts as a corrosion barrier and upon ageing the Al4Ce phase precipitates along the α grain boundaries. The precipitation modifies the β phase to form more continuous network which subsequently reduces the corrosion attack in the chlorine environment. Salt spray test result shows the AZ61 alloy with 1.5 wt% Ce aged at 220 °C exhibits the better corrosion resistance.

Abstract Background To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). Methods CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. Results 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. Conclusions Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics.

Background: The COVID-19 pandemic overburdened the healthcare system and affected the mental health of healthcare workers. Yoga has proven to improve mental health correlates, within diverse population groups, including healthcare workers. Considering the pandemic-imposed restrictions, this trial was designed to study the feasibility and effect of tele-yoga intervention on burnout, sleep quality, depression, anxiety, stress, mindfulness, and immune markers of healthcare workers on COVID-19 duty., Methods: This randomized controlled trial was conducted in a tertiary care hospital. Tele-yoga intervention was delivered five days a week for 8 weeks. Stanford Professional Fulfilment Index (SPFI), Pittsburg Sleep Quality Index (PSQI), Depression Anxiety and Stress Scale (DASS-21), Mindfulness Attention Awareness Scale (MAAS) were used to assess the burnout, sleep quality, depression, anxiety, stress and mindfulness. Blood samples were assessed for TNF-α, IL-6 and serum cortisol levels., Results: A total of 147 healthcare workers were screened to achieve a sample size of 90 (45 each in tele-yoga intervention and control group). Of the 45 subjects in the intervention group, 35 attended at least 50 % of sessions over 8 weeks, at the rate of 3.35 sessions per week. Nearly 37.14 % of subjects among 35 were able to attend more than 70 % of the tele-yoga sessions. At the endline, 35 in the intervention and 37 in the control group completed the outcome questionnaires. On both per protocol (PPA) and intention to treat analyses (ITT) the burnout index, PSQI, anxiety and stress scores and IL-6 and serum cortisol level were significantly lower among the tele-yoga group compared to control group participants (p<0.05) at the endline. The effect size was medium (r=0.3-0.5) favoring intervention group for most of the parameters., Conclusions: Tele-yoga is a feasible and accessible intervention for improving burnout, sleep quality, and reducing anxiety, stress, IL-6, and serum cortisol among healthcare workers in tertiary care hospitals during the COVID-19 pandemic. Being a single-center pilot study in India and with other methodological limitations, the generalizability of the study findings is restricted., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Sedentary behavior is highly prevalent and associated with morbidity and mortality in chronic kidney disease (CKD). A Sit Less, Interact and Move More (SLIMM) sedentary activity coaching intervention can reduce sedentary duration among persons with CKD, but preliminary data suggest that effects may not persist. Prior studies have suggested that moderate/vigorous intensity physical activities are not sustainable in persons with CKD. Therefore, we aimed to determine whether guided resistance training ± oral semaglutide co-intervention improves adherence and/or persistence of the SLIMM intervention., Method/design: The SLIMM-2 is a two-center study designed with a 3-month sedentary activity coaching (SLIMM) followed by a 9-month randomized controlled trial with three arms: SLIMM + standard of care resistance training + oral placebo, SLIMM + guided resistance training + oral placebo, or SLIMM + guided resistance training + oral semaglutide. The study is recruiting persons with CKD (eGFR 20 to ≤60 ml/min/1.73 m 2 ). ActivPAL, a wearable tri-axial accelerometer, is used to assess outcomes including sedentary duration (primary outcome), stepping duration and the average number of steps per day. Additional outcomes include 6-min walk distance and body fat percentage. Persons randomized to standard of care resistance training will be encouraged to maintain individualized physical activity goals; those randomized to guided resistance training will attend guided sessions per month and be prescribed daily independent exercises., Results: Enrollment, interventions, and follow-up are ongoing., Conclusions: Results from the SLIMM-2 study are expected to inform clinical practice, with the potential to enhance physical health and functioning among persons with CKD., (Copyright © 2024. Published by Elsevier Inc.)

Microbial cellulases have become significant biocatalysts because of their complex composition and extensive industrial applications. This study aimed to isolate an efficient cellulase-producing strain, followed by molecular identification, enzyme purification, and characterization. Among 110 isolates, Bacillus amyloliquefaciens OKB3 was selected for its significant cellulase production, with optimal activity at pH 5.0 and 34 °C. The purification using ammonium sulfate and Sephadex G-100 chromatography resulted in specific activity of 2720.76 U/mg, 2.91 fold purification, and 29.44 % yield. The purified cellulase named CelB was a dimeric macromolecule of 123 kDa consisting of 67 and 54 kDa subunits. CelB was most active at 60 °C and pH 6, and it was stable at pH 5.5 to 6.0 and 0 °C to 4 °C. CelB was unaffected by metal cofactors and inhibited in the presence of divalent cations Cu 2+ , Hg 2+ , Cd 2+ , and Ag 2+ . The CelB has higher specificity of CMC compared to other substrates. The K m , V max, and K cat values were 0.037 mM, 188.67 μmole/min, and 7430 S -1 respectively. The unique attributes of CelB make it a very promising candidate for various biotechnological applications., 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 © 2024. Published by Elsevier B.V.)

The development of new efficient materials for the removal of water-soluble toxic organic dyes has been one of the focused research areas in the recent past. There is a strong demand for the new materials as most of the reported techniques/materials suffer from serious limitations. In this regard, a series of flexible chitosan-based task-specific polyurethane foams (PUCS-GP, PUCS-CA-GP, PUCS-TA-GP, and PUCS-GA-GP) associated with naturally available hydroxycarboxylic acids was developed. The basis for the preparation of these task-specific and functionalized PU foams is to possess amine groups for trapping the anionic dyes (example: Orange II denoted as OII) and carboxylic acid groups for attracting the cationic dyes (example: Rhodamine B denoted as RhB) under specified pH conditions. Batch adsorption experiments were conducted to assess and improve various parametric conditions. The experimental results revealed that the adsorption kinetics closely agree with the pseudo-second-order model having a maximum sorption capacity of 38.3 mg/g at pH 3 for OII on PUCS-GP and 48.4 mg/g at pH 6 for RhB on PUCS-CA-GP. Furthermore, the adsorption process was described by isotherms, kinetic equations and thermodynamic parameters (ΔG°, ΔH° and ΔS°). Notably, the regeneration of OII and RhB dyes from the exhausted PUCS-GP and PUCS-CA-GP materials was effectively accomplished. The recovered PUCS-GP shows >90 % OII and PUCS-CA-GP displays >70 % RhB removal efficiency even after twelve adsorption-desorption processes under mild conditions, demonstrating excellent recyclability/durability. The advantages of these functionalized foam materials are facile preparation, high adsorption capacity, good reusability, and very efficient removal of organic dyes from wastewater streams., 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 © 2024 Elsevier B.V. All rights reserved.)

Introduction: The current evidence linking tooth loss and cardiovascular disease mortality is inconclusive. Thus, the aim of this systematic review was to explore the association between tooth loss and cardiovascular disease (CVD) mortality., Methods: A comprehensive literature search of databases and gray literature included: Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, various digital repositories. The included studies reported on CVD mortality and tooth loss. The Newcastle-Ottawa scale was used to assess the quality of included studies. Random-effects meta-analysis method, sub-group analysis (based on the tooth loss categories (edentulous and fewer than 10 teeth present), meta-regression (based on the number. of confounders), publication bias, and sensitivity analysis were performed., Results: Twelve articles met the eligibility criteria with an overall "Good" quality. A significant association between tooth loss (edentulous or less than 10 teeth present) and CVD mortality was found in the primary meta-analysis, which compiled data from 12 studies. The estimated hazard ratio was 1.66 (95% CI: 1.32-2.09), and there was high heterogeneity (I 2  = 82.42). Subgroup analysis revealed that the edentulous subgroup showed a higher risk with no significant heterogeneity, while the subgroup with fewer than 10 teeth showed a higher risk with substantial heterogeneity. Meta-regression analysis did not reveal any significant impact (P = .626) on whether variations in the number of confounders across studies would substantially affect the overall findings. No publication bias was detected and the sensitivity analysis based on the critical confounders also confirmed that tooth loss as a risk factor for CVD mortality (hazard ratio = 1.52, 95% CI: 1.28-1.80), (I 2  51.82%)., Conclusion: The present systematic review reported that being edentulous or having lesser than 10 teeth is a predictive indicator of CVD mortality., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with non-alcoholic fatty liver disease (NAFLD) is not well-understood. We prospectively defined rates of progression to and regression from LSM-defined compensated advanced chronic liver disease (cACLD) and their associations with liver-related events (LREs)., Methods: Participants in the NASH Clinical Research Network-led NAFLD Database 2 and 3 studies were included. Progression to cACLD was defined as reaching LSM ≥10 kPa in participants with LSM <10 kPa on initial VCTE; regression from cACLD was defined as reaching LSM <10 kPa in participants with baseline LSM ≥10 kPa. LREs were defined as liver-related death, liver transplant, hepatocellular carcinoma, MELD >15, development of varices, or hepatic decompensation. Univariate and multivariable interval-censored Cox regression analyses were used to compare the cumulative LRE probability by LSM progression and regression status., Results: In 1,403 participants, 89 LREs developed over a mean follow-up of 4.4 years, with an annual incidence rate for LREs of 1.5 (95% CI 1.2-1.8). In participants at risk, progression to LSM ≥10 or ≥15 kPa occurred in 29% and 17%, respectively, whereas regression to LSM <10 or <15 kPa occurred in 44% and 49%, respectively. Progressors to cACLD (≥10 kPa) experienced a higher cumulative LRE rate vs. non-progressors (16% vs. 4%, adjusted hazard ratio 4.0; 95% (1.8-8.9); p <0.01). Regressors from cACLD (to LSM <10 kPa) experienced a lower LRE rate than non-regressors (7% vs. 32%, adjusted hazard ratio 0.25; 95% CI 0.10-0.61; p <0.01)., Conclusions: Change in LSM over time is independently and bi-directionally associated with risk of LRE and is a non-invasive surrogate for clinical outcomes in patients with NAFLD., Impact and Implications: The prognostic value of change in LSM in patients with NAFLD is not well understood. In this large prospective study of patients with NAFLD and serial vibration-controlled transient elastography exams, baseline and dynamic changes in LSM were associated with the risk of developing liver-related events. LSM is a useful non-invasive surrogate of clinical outcomes in patients with NAFLD., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance. The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m 6 A) modification. m 6 A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m 6 A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases. Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m 6 A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Complete valorization of lignocellulosic biomass is crucial for bio-based biorefineries to fulfil the circular bioeconomy concept. However, the existence of lignin carbohydrate complexes (LCC) in biomass hinders the simultaneous fractionation of biomass components, such as lignin, hemicellulose and cellulose, for subsequent biorefining processes. This study explores for the first time a novel approach tailored for the deconstruction of sorghum biomass components through efficient breakdown of LCC. Selective targeting of the major LCC linkages binding xylan and lignin was performed using an ultrasound-assisted deep eutectic solvent under mild treatment conditions. This process yielded a maximum cellulose content of 98.3 %, hemicellulose content of 95.2 %, and lignin content of 94.6 %, with the highest purities of 99.43 %, 96.71 %, and 98.12 %, respectively. FTIR, 2D-HSQC NMR and XRD analyses confirmed that most of the structural properties of lignin, hemicellulose, cellulose are retained. The lignocellulosic components were successfully valorised to cellulose, hemicellulose, and lignin nanoparticles with mean sizes of 64.5 ± 6 nm, 72.8 ± 4 nm and 57.2 ± 8 nm respectively, with good thermal stability. The proposed green process enables the complete utilization of agro-residue feedstock for the preparation of biomass-derived nanoparticles, thereby accelerating the economic and industrial prospects of bio-based biorefineries., 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 © 2024. Published by Elsevier B.V.)

The pathophysiological link between diabetes and heightened propensity for the development of coronary heart disease (CHD) is well-established. Prevailing evidence confirms that small increases in low concentrations of high-sensitivity C reactive protein (hs-CRP) in the human body can determine the tendency of developing CHD. Additionally, glycated hemoglobin (HbA1c) is a well-recognized biomarker to evaluate diabetes progression. Given the positive correlation between diabetes and CHD, this research presents a notably unprecedented label-free electrochemical approach for the dual detection of %HbA1c regarding Total Hb and hs-CRP, facilitating early CHD prediction and cost-effective point-of-care diagnostics. Furthermore, a novel redox probe O-(4-Nitrophenylphosphoryl)choline (C 11 H 17 N 2 O 6 P) was used for the electrochemical detection of CRP, a method not documented in scientific literature before. The calibration curves demonstrate a limit of detection (LOD) of 5 mg/mL in PBS (pH 8) and 6 mg/mL in simulated blood (SB) for a linear range of 0-30 mg/mL of HbA1c. Conjointly, a LOD of 0.007 mg/mL and 0.008 mg/mL for measurement in PBS (pH 7.4) and SB are reported for a linear range of 0-0.05 mg/mL of CRP. The electrochemical systems presented could accurately quantify HbA1c and CRP in mixed samples, demonstrating reasonable specificity and practical applicability for complex biological samples., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Children with ASD experience significant gross motor challenges that could be addressed using motor interventions. However, contemporary ASD interventions that are sedentary in nature often target communication and fine motor skills and not children's gross motor difficulties., Methods: In the current pilot RCT, we evaluated changes in various motor outcomes (i.e., gross/fine motor coordination, locomotor skills, functional endurance, and praxis/imitation performance) following two types of whole-body motor interventions (Creative Movement (CM) or General Movement (GM)) and compared them to a Sedentary Play (SP) intervention focused on improving fine motor skills in children with ASD. Forty-five children with ASD (Mean Age ±SE: 8.7 ± 0.3, 38 males) were randomly assigned to the CM, GM, or SP groups and received 8 weeks of group-specific training., Results: Both CM and GM interventions led to medium-to-large improvements in gross motor performance, including improved body coordination, strength/agility, locomotor skills, and walking endurance. Children in the CM group additionally showed medium-to-large-sized improvements in praxis performance, while children in the SP group showed improvements in fine motor performance. These training-related improvements were supported by improvements reported via parental questionnaires., Conclusions: Researchers and clinicians should incorporate whole-body interventions targeting gross motor skills in the plan of care for children with ASD., Competing Interests: Conflict of Interest The authors have no conflict of Interest to declare. Declaration of Competing Interest All authors have no financial or other conflicts of interest to report.

The pandemic of COVID-19 has imposed tremendous pressure on public health systems and social economic ecosystems over the past years. To alleviate its social impact, it is important to proactively track the prevalence of COVID-19 within communities. The traditional way to estimate the disease prevalence is to estimate from reported clinical test data or surveys. However, the coverage of clinical tests is often limited and the tests can be labor-intensive, requires reliable and timely results, and consistent diagnostic and reporting criteria. Recent studies revealed that patients who are diagnosed with COVID-19 often undergo fecal shedding of SARS-CoV-2 virus into wastewater, which makes wastewater-based epidemiology for COVID-19 surveillance a promising approach to complement traditional clinical testing. In this paper, we survey the existing literature regarding wastewater-based epidemiology for COVID-19 surveillance and summarize the current advances in the area. Specifically, we have covered the key aspects of wastewater sampling, sample testing, and presented a comprehensive and organized summary of wastewater data analytical methods. Finally, we provide the open challenges on current wastewater-based COVID-19 surveillance studies, aiming to encourage new ideas to advance the development of effective wastewater-based surveillance systems for general infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests of personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: Ferroportin (Fpn) is the only iron exporter, playing a crucial role in systemic iron homeostasis. Fpn is negatively regulated by its ligand hepcidin, but other potential regulators in physiological and disease conditions remain poorly understood. Diabetes is a metabolic disorder that develops body iron loading with unknown mechanisms. By using diabetic mouse models and human duodenal specimens, we demonstrated that intestinal Fpn expression was increased in diabetes in a hepcidin-independent manner. Protein kinase C (PKC) is hyperactivated in diabetes. We showed that PKCα was required to sustain baseline Fpn expression and diabetes-induced Fpn upregulation in the enterocytes and macrophages. Knockout of PKCα abolished diabetes-associated iron overload. Mechanistically, activation of PKCα increased the exocytotic trafficking of Fpn and decreased the endocytic trafficking of Fpn in the resting state. Hyperactive PKCα also suppressed hepcidin-induced ubiquitination, internalization, and degradation of Fpn. We further observed that iron loading in the enterocytes and macrophages activated PKCα, acting as a novel mechanism to enhance Fpn-dependent iron efflux. Finally, we demonstrated that the loss-of-function of PKCα and pharmacological inhibition of PKC significantly alleviated hereditary hemochromatosis-associated iron overload. Our study has highlighted, to our knowledge, for the first time, that PKCα is an important positive regulator of Fpn and a new target in the control of iron homeostasis.

Competing Interests: Declaration of Competing Interest None.

UVA-EpiHiper is a national scale agent-based model to support the US COVID-19 Scenario Modeling Hub (SMH). UVA-EpiHiper uses a detailed representation of the underlying social contact network along with data measured during the course of the pandemic to initialize and calibrate the model. In this paper, we study the role of heterogeneity on model complexity and resulting epidemic dynamics using UVA-EpiHiper. We discuss various sources of heterogeneity that we encounter in the use of UVA-EpiHiper to support modeling and analysis of epidemic dynamics under various scenarios. We also discuss how this affects model complexity and computational complexity of the corresponding simulations. Using round 13 of the SMH as an example, we discuss how UVA-EpiHiper was initialized and calibrated. We then discuss how the detailed output produced by UVA-EpiHiper can be analyzed to obtain interesting insights. We find that despite the complexity in the model, the software, and the computation incurred to an agent-based model in scenario modeling, it is capable of capturing various heterogeneities of real-world systems, especially those in networks and behaviors, and enables analyzing heterogeneities in epidemiological outcomes between different demographic, geographic, and social cohorts. In applying UVA-EpiHiper to round 13 scenario modeling, we find that disease outcomes are different between and within states, and between demographic groups, which can be attributed to heterogeneities in population demographics, network structures, and initial immunity., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This review provides a comprehensive overview of the latest advancements in wearable biosensors, emphasizing their applications in cardiovascular disease monitoring. Initially, the key sensing signals and biomarkers crucial for cardiovascular health, such as electrocardiogram, phonocardiography, pulse wave velocity, blood pressure, and specific biomarkers, are highlighted. Following this, advanced sensing techniques for cardiovascular disease monitoring are examined, including wearable electrophysiology devices, optical fibers, electrochemical sensors, and implantable cardiac devices. The review also delves into hydrogel-based wearable electrochemical biosensors, which detect biomarkers in sweat, interstitial fluids, saliva, and tears. Further attention is given to flexible electronics-based biosensors, including resistive, capacitive, and piezoelectric force sensors, as well as resistive and pyroelectric temperature sensors, flexible biochemical sensors, and sensor arrays. Moreover, the discussion extends to polymer-based wearable sensors, focusing on innovations in contact lens, textile-type, patch-type, and tattoo-type sensors. Finally, the review addresses the challenges associated with recent wearable biosensing technologies and explores future perspectives, highlighting potential groundbreaking avenues for transforming wearable sensing devices into advanced diagnostic tools with multifunctional capabilities for cardiovascular disease monitoring and other healthcare applications., 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 © 2024 Elsevier B.V. All rights reserved.)

The taxonomic position and genomic characteristics of a nitrogen fixing and polymer degrading marine bacterium, strain SAOS 164 isolated from a mangrove sediment sample was investigated. Sequence analysis based on 16S rRNA gene identified it as a member of family Halieaceae with closest similarity to Haliea salexigens DSM 19537 T (96.3 %), H. alexandrii LZ-16-2 T (96.2 %) and Parahaliea maris HSLHS9 T (96.0 %) but was distantly related to the genera Haliea, Parahaliea and Halioglobus in phylogenetic trees. In order to ascertain the exact taxonomic position, phylogeny based on RpoBC proteins, whole genome, core and orthologous genes, and comparative analysis of metabolic potential retrieved the strain in an independent lineage clustering along with the genera Halioglobus, Pseudohalioglobus and Seongchinamella. Further, various genome based delimitation parameters represented by mol % GC content, percentage of conserved proteins (POCP), and amino acid identity (AAI) along with chemotaxonomic markers (i.e. fatty acids and polar lipids) supported the inferences of genome based phylogeny and indicated that the strain SAOS 164 belongs to a novel genus. The genome was mapped to 4.8 Mb in size with 65.1 % DNA mol% G + C content. In-silico genomic investigation and phenotyping revealed diverse metabolite genes/pathways related to polymer hydrolysis, nitrogen fixation, light induced growth, carbohydrate, sulfur, phosphorus and amino acid metabolism, virulence factors, defense mechanism, and stress-responsive elements facilitating survival in the mangrove habitat. Based on polyphasic taxonomic approach including genome analyses, a novel genus Mangrovimicrobium sediminis gen. nov. sp. nov. (=SAOS 164 T  = MTCC 12907 T  = KCTC 52755 T  = JCM 32136 T ) is proposed. Additionally, the reclassification of Halioglobus pacificus (=DSM 27932 T  = KCTC 23430 T  = S1-72 T ) to Pseudhalioglobus pacificus comb. nov. is also proposed., 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 © 2024 Elsevier B.V. All rights reserved.)

Artificial nanozymes (enzyme-mimics), specifically metallic nanomaterials, have garnered significant attention recently due to their reduced preparation cost and enhanced stability in a wide range of environments. The present investigation highlights, for the first time, a straightforward green synthesis of biogenic platinum nanoparticles (PtNPs) from a natural resource, namely Prunella vulgaris (Pr). To demonstrate the effectiveness of the phytochemical extract as an effective reducing agent, the PtNPs were characterized by various techniques such as UV-vis spectroscopy, High-resolution Transmission electron microscopy (HR-TEM), zeta-potential analysis, Fourier-transform infrared spectroscopy (FTIR), and Energy dispersive spectroscopy (EDS). The formation of PtNPs with narrow size distribution was verified. Surface decoration of PtNPs was demonstrated with multitudinous functional groups springing from the herbal extract. To demonstrate their use as viable nanozymes, the peroxidase-like activity of Pr/PtNPs was evaluated through a colorimetric assay. Highly sensitive visual detection of H 2 O 2 with discrete linear ranges and a low detection limit of 3.43 μM was demonstrated. Additionally, peroxidase-like catalytic activity was leveraged to develop a colorimetric platform to quantify glutamate biomarker levels with a high degree of selectivity, the limit of detection (LOD) being 7.00 μM. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) test was used to explore the scavenging nature of the PtNPs via the degradation of DPPH. Overall, the colorimetric assay developed using the Pr/PtNP nanozymes in this work could be used in a broad spectrum of applications, ranging from biomedicine and food science to environmental monitoring., Competing Interests: Declaration of competing interest The author declare that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)