Self-Assembled Conjugated Coordination Polymer Nanorings: Role of Morphology and Redox Sites for the Alkaline Electrocatalytic Oxygen Evolution Reaction.

Electrocatalytic water splitting provides a sustainable method for storing intermittent energies, such as solar energy and wind, in the form of hydrogen fuel. However, the oxygen evolution reaction (OER), constituting the other half-cell reaction, is often considered the bottleneck in overall water splitting due to its slow kinetics. Therefore, it is crucial to develop efficient, cost-effective, and robust OER catalysts to enhance the water-splitting process. Transition-metal-based coordination polymers (CPs) serve as promising electrocatalysts due to their diverse chemical architectures paired with redox-active metal centers. Despite their potential, the rational use of CPs has faced obstacles including a lack of insights into their catalytic mechanisms, low conductivity, and morphology issues. Consequently, achieving success in this field requires the rational design of ligands and topological networks with the desired electronic structure. This study delves into the design and synthesis of three novel conjugated coordination polymers (CCPs) by leveraging the full conjugation of terpyridine-attached flexible tetraphenylethylene units as electron-rich linkers with various redox-active metal centers [Co(II), Ni(II), and Zn(II)]. The self-assembly process is tuned for each CCP, resulting in two distinct morphologies: nanosheets and nanorings. The electrocatalytic OER performance efficiency is then correlated with factors such as the nanostructure morphology and redox-active metal centers in alkaline electrolytes. Notably, among the three morphologies studied, nanorings for each CCP exhibit a superior OER activity. Co(II)-integrated CCPs demonstrate a higher activity between the redox-active metal centers. Specifically, the Co(II) nanoring morphology displays exceptional catalytic activity for OER, with a lower overpotential of 347 mV at a current density of 10 mA cm-2 and small Tafel slopes of 115 mV dec-1. The long-term durability is demonstrated for at least 24 h at 1.57 V vs RHE during water splitting. This is presumably the first proof that links the importance of nanostructure morphologies to redox-active metal centers in improving the OER activity, and it may have implications for other transdisciplinary energy-related applications.

Up-regulation of extracellular-matrix and inflammation related genes in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy with late-presentation, site-specific heterogeneity, and high-propensity for recurrence/metastasis that has shown rise in mortality. Lately, research emphasize on dynamic interactions between tumor-cells and extracellular-matrix components within tumor-microenvironment that promote tissue integrity loss and carcinogenesis. Therefore, OSCC clinical-management is still challenging. DESIGN: Present study validated clinical utility of a 13 gene-panel in two chief sub-sites of OSCC: Buccal mucosa squamous cell carcinoma (BMSCC) (N = 50) and Tongue squamous cell carcinoma (TSCC) (N = 52) using qRT-PCR. Principal component analysis and binary logistic regression analysis were applied to acquire definite multi gene models. Protein expression analysis was employed using the Human Protein Atlas, UALCAN and TIMER 2.0 databases to explore potential correlation between immune cells and gene-panels. RESULTS: Significant up-regulation of CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, PLAU, SERPINE1 and SPP1 except OASL was observed in OSCC tissue in comparison of absolute normal controls. Although, this gene-panel could potentially discriminate OSCC tissues from absolute normal controls as solitarily diagnostic and/or predictive biomarkers, models generated also showed substantial discriminating efficacy. Eight-genes were found to be significantly associated with poor-prognosis on clinico-pathological association. Protein-expression confirmed overexpression of gene-panel and added advantage of being secretory-protein. Importantly, up-regulated genes in our study showed significant relation with immune-cells infiltration suggesting their contribution in immune-escape. CONCLUSION: Thus, we propose that the 13 gene-panel could pave the way to effective and personalized clinical-management of OSCC in terms of diagnostic and prognostic measures and thereby as therapeutic targets.

Neural Correlates of the p Factor in Adolescence: Cognitive Control With and Without Enhanced Positive Affective Demands.

BACKGROUND: Recent research has aimed to characterize processes underlying general liability toward psychopathology, termed the p factor. Given previous research linking the p factor with difficulties in both executive functioning and affective regulation, the present study investigated nonaffective and positive affective inhibition in the context of a sustained attention/inhibition paradigm in adolescents exhibiting mild to severe psychopathology. METHODS: Functional magnetic resonance imaging data were collected during an integrated reward conditioning and go/no-go task in 138 adolescents assigned female at birth. We modeled the p factor using hierarchical confirmatory factor analysis. Positive affective inhibition was measured by examining responses to no-go stimuli with a history of reward conditioning. We examined associations between p factor scores and neural function and behavioral performance. RESULTS: Consistent with nonaffective executive function as a primary risk factor, p factor scores were associated with worse behavioral performance and hypoactivation in the left superior frontal gyrus and middle frontal gyrus during response initiation (go trials). The p factor scores were additionally associated with increased error-related signaling in the temporal cortex during incorrect no-go trials. CONCLUSIONS: During adolescence, a period characterized by heightened risk for emergent psychopathology, we observed unique associations between p factor scores and neural and behavioral indices of response initiation, which relies primarily on sustained attention. These findings suggest that shared variation in mental disorder categories is characterized in part by sustained attention deficits. While we did not find evidence that the p factor was associated with inhibition in this study, this observation is consistent with our hypothesis that the p factor would be related to nonaffective control processes.

Neural Markers of Emotion Reactivity and Regulation Before and After a Targeted Social Rejection: Differences Among Girls With and Without Suicidal Ideation and Behavior Histories.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are common among adolescent girls and increase risk for suicide death. Emotion regulation difficulties are linked with STBs, particularly in response to targeted social rejection. However, neural correlates of this link have not been investigated and may identify novel targets for interventions. Here, we examined neural correlates of emotion regulation before and after an experimentally delivered targeted social rejection in adolescent girls with STBs and girls without STBs (i.e., control participants). METHODS: Girls (N = 138; age range, 9-15 years; mean [SD] age = 11.6 [1.79] years) completed a functional neuroimaging emotion regulation task. In the middle of the task, participants were socially rejected by an unfamiliar confederate whom the participants had elected to meet. Participants also completed a multimethod STB assessment. RESULTS: Before rejection, girls with a history of STBs, compared with control participants, showed greater activation in the right superior frontal gyrus when passively viewing negative stimuli, and girls with suicidal behavior (SB) versus those without SB showed less activation in the right frontal pole during emotion regulation attempts. Following the rejection, girls with STBs, compared with control participants, showed greater activation in the right inferior frontal gyrus during emotion regulation. CONCLUSIONS: Before social rejection, girls with SB versus without SB may not activate brain regions implicated in emotion regulation, suggesting a vulnerability to poor regulation at their baseline emotional state. After social rejection, girls with any history of STBs showed altered activation in a brain region strongly associated with inhibition and emotion regulation success, possibly reflecting increased effort at inhibiting emotional responses during regulation following stress exposure.

Melatonin: Emerging Player in the Management of Oral Cancer.

Oral cancer (OC) has emerged as a major medical and social issue in many industrialized nations due to the high death rate. It is becoming increasingly common in people under the age of 45, although the underlying causes and mechanisms of this increase remain unclear. Melatonin, as a pleiotropic hormone, plays a pivotal role in a wide variety of cellular and physiological functions. Mounting evidence supports melatonin's ability to modify/influence oral carcinogenesis, help in the reduction of the incidence of OC, and increase chemo- and radiosensitivity. Despite its potential anti-carcinogenic effects, the precise function of melatonin in the management of OC is not well understood. This review summarizes the current knowledge regarding melatonin function in anti-carcinogenesis mechanisms for OC. In addition, clinical assessment and the potential therapeutic utility of melatonin in OC are discussed. This review will provide a basis for researchers to create new melatonin-based personalized medicines for treating and preventing OC.

Plastic Chip Electrode: An Emerging Multipurpose Electrode Platform.

The properties of electrodes play a crucial role in the processes occurring on them. Therefore, a variety of materials have been tried as electrodes. Carbon composite materials are among the most admired ones. Use of composites as electrode material dates back to the mid of the last century when polymer-carbon composites were tried as general-purpose electrode platforms and epoxy impregnated graphite paste/ solid electrodes were tried in polarography. Later the composite electrodes have seen several phases of development. Plastic Chip Electrode (PCE) is a class of polymer composite electrode developed by our group. This monographic review gives a bird's eye account of polymer composite electrodes and appurtenant work, followed by elaborating on various aspects and state-of-the-art plastic chip electrodes.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Novavax COVID-19 Vaccine (NVX-CoV2373), a recombinant spike protein vaccine with Matrix-M adjuvant to prevent disease caused by SARS-CoV-2 viruses.

Novavax, a global vaccine company, began evaluating NVX-CoV2373 in human studies in May 2020 and the pivotal placebo-controlled phase 3 studies started in November 2020; five clinical studies provided adult and adolescent clinical data for over 31,000 participants who were administered NVX-CoV2373. This extensive data has demonstrated a well-tolerated response to NVX-CoV2373 and high vaccine efficacy against mild, moderate, or severe COVID-19 using a two-dose series (Dunkle et al., 2022) [1], (Heath et al., 2021) [2], (Keech et al., 2020) [3], (Mallory et al., 2022) [4]. The most common adverse events seen after administration with NVX-CoV2373 were injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, nausea, or vomiting. In addition, immunogenicity against variants of interest (VOI) and variants of concern (VOC) was established with high titers of ACE2 receptor-inhibiting and neutralizing antibodies in these studies (EMA, 2022) [5], (FDA, 2023) [6]. Further studies on correlates of protection determined that titers of anti-Spike IgG and neutralizing antibodies correlated with efficacy against symptomatic COVID-19 established in clinical trials (p < 0.001 for recombinant protein vaccine and p = 0.005 for mRNA vaccines for IgG levels) (Fong et al., 2022) [7]. Administration of a booster dose of the recombinant protein vaccine approximately 6 months following the primary two-dose series resulted in substantial increases in humoral antibodies against both the prototype strain and all evaluated variants, similar to or higher than the antibody levels observed in phase 3 studies that were associated with high vaccine efficacy (Dunkle et al., 2022) [1], (Mallory et al., 2022) [4]. These findings, together with the well tolerated safety profile, support use of the recombinant protein vaccine as primary series and booster regimens.

Surgical Aortic Valve Replacement to Treat Prosthetic Valve Endocarditis After Valve-in-Valve Transcatheter Aortic Valve Replacement.

Prosthetic valve endocarditis (PVE) is an uncommon complication after heart valve replacement surgery that can result in increased morbidity and mortality. Current guidelines for management of PVE recommend antibiotic therapy followed by surgical valve replacement. The number of aortic valve replacements is expected to rise in the coming years with the expanded indications for use of transcatheter aortic valve replacement (TAVR) in patients with low, intermediate, and high surgical risk, as well as in patients with a failed aortic bioprosthetic valve. Current guidelines do not address the use of valve-in-valve (ViV) TAVR for management of PVE in patients who are at high risk for surgical intervention. The authors present a case of a patient with aortic valve PVE after surgical aortic valve replacement (SAVR); he was treated with valve-in-valve (ViV) TAVR due to the high surgical risk. The patient was discharged, but he returned to the hospital with PVE and valve dehiscence 14 months after ViV TAVR, after which he successfully underwent re-operative SAVR.

Association of Interactions between Metabolic 'Caretaker' Genes, p53, MDM2, and Tobacco Use with the Risk of Oral Cancer: A Multifactor Dimensionality Reduction Approach.

BACKGROUND: The present study investigated the association of interactions between gene polymorphisms in metabolic 'caretaker' genes (Phase I: CYP1A1, CYP2E1; Phase II: GSTM1, GSTT1), the cell cycle regulatory gene, p53, along with its negative controller, MDM-2, and the environment variable (tobacco). A nonparametric model, multifactor dimensionality reduction (MDR), was applied to analyse these interactions. MATERIALS AND METHODS: This case-control study was carried out on 242 subjects. Genomic DNA was extracted from peripheral blood lymphocytes.11 gene variants with an exposure variable (tobacco use) were analysed using MDR to identify the best locus model for gene-gene and gene-environment interactions. Statistical significance was evaluated using a 1000-fold permutation test using MDR permutation testing software (version 1.0 beta 2). The value of p<0.05 was considered statistically significant. RESULTS: The best three-locus model for gene-gene interaction included two of the p53 gene polymorphisms; rs17878362 (intron 3) and rs1042522 (exon 4) and rs6413432 in the Phase I gene, CYP2E1(DraI). The three-locus model to evaluate the gene-environment interaction included two intronic polymorphisms of the p53 gene, that is, rs17878362 (intron 3) and rs1625895 (intron 6), and rs4646903 in the Phase I gene CYP1A1*2C. The interaction graphs revealed independent main effects of the tobacco and p53 polymorphism, rs1042522 (exon 4), and a significant additive interaction effect between rs17878362 (intron 3) and rs1042522 (exon 4). CONCLUSIONS: The nonparametric approach highlighted the potential role of tobacco use and variations in the p53 gene as significant contributors to oral cancer risk. The findings of the present study will help implement preventive strategies in both tobacco use and screening using a molecular pathology approach.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood.

OBJECTIVE: The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD: The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. RESULTS: Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. CONCLUSION: Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

Primary cilia, A-kinase anchoring proteins and constitutive activity at the orphan G protein-coupled receptor GPR161: A tale about a tail.

Primary cilia are non-motile antennae-like structures responsible for sensing environmental changes in most mammalian cells. Ciliary signalling is largely mediated by the Sonic Hedgehog (Shh) pathway, which acts as a master regulator of ciliary protein transit and is essential for normal embryonic development. One particularly important player in primary cilia is the orphan G protein-coupled receptor, GPR161. In this review, we introduce GPR161 in the context of Shh signalling and describe the unique features on its C-terminus such as PKA phosphorylation sites and an A-kinase anchoring protein motif, which may influence the function of the receptor, cAMP compartmentalisation and/or trafficking within primary cilia. We discuss the recent putative pairing of GPR161 and spexin-1, highlighting the additional steps needed before GPR161 could be considered 'deorphanised'. Finally, we speculate that the marked constitutive activity and unconventional regulation of GPR161 may indicate that the receptor may not require an endogenous ligand.

Solubility Enhancement and Inhalation Delivery of Cyclodextrin-Based Inclusion Complex of Delamanid for Pulmonary Tuberculosis Treatment.

Tuberculosis (TB) is a contiguous airborne disease caused by Mycobacterium tuberculosis (M.tb), primarily affecting the human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become a global challenge toward eradicating TB. Conventional TB treatment involves frequent dosing and prolonged treatment regimens predominantly by an oral or invasive route, leading to treatment-related systemic adverse effects and patient's noncompliance. Pulmonary delivery is an attractive option as we could reduce dose, limit systemic side-effects, and achieve rapid onset of action. Delamanid (DLD), an antituberculosis drug, has poor aqueous solubility, and in this study, we aim to improve its solubility using cyclodextrin complexation. We screened different cyclodextrins and found that HP-ß-CD resulted in a 54-fold increase in solubility compared to a 27-fold and 13-fold increase by SBE-ß-CD and HP-É£-CD, respectively. The stability constant (265 ± 15 M-1) and complexation efficiency (8.5 × 10-4) suggest the formation of a stable inclusion complex of DLD and HP-ß-CD in a 2:1 ratio. Solid-state characterization studies (DSC, PXRD, and NMR) further confirmed successful complexation of DLD in HP-ß-CD. The nebulized DLD-CD complex solution showed a mass median aerodynamic diameter of 4.42 ± 0.62 µm and fine particle fraction of 82.28 ± 2.79%, suggesting deposition in the respiratory airways. In bacterial studies, minimum inhibitory concentration of DLD-CD complex was significantly reduced (four-fold) compared to free DLD in M.tb (H37Ra strain). Furthermore, accelerated stability studies confirmed that the inclusion complex was stable for 4 weeks with 90%w/w drug content. In conclusion, we increased the aqueous solubility of DLD through cyclodextrin complexation and improved its efficacy in vitro.

Inpatient rehabilitation wheelchair management quality improvement project: Implications for patients with spinal cord injury.

Context/Objective: Evaluate hospital fleet wheelchair (WC) requests submitted by physical therapists (PT) for patients with spinal cord injury (SCI) to trial and use during inpatient rehabilitation.Design: Quality improvement project secondary analysis of delivery process and WC trials.Setting: Urban inpatient rehabilitation hospital.Participants: Internal review of 4,371 WC requests narrowed to 750 patients with SCI.Interventions: PTs submitted WC requests between March 25, 2017, and September 30, 2019.Outcome Measures: WC delivery timeframe, level of SCI, type of WC.Results: PTs requested power (28%), and manual WC bases: standard (19.1%), tilt (18.9%), ultralight rigid (18.9%), ultralight folding (13.5%), and recliner (1.6%) respectively. Patients received fleet WCs 49.9% of the time within specified urgency timeframes. A Chi-Square test showed a significant association between WC request urgency and fulfillment within established timeframes (χ2 = 19.68, P < 0.001, n = 750). Broken down by urgency level: 60.0% low (n = 12), 56.2% medium (n = 244), and 39.9% high (n = 118) received their WC within established timeframes. Patients with cervical level SCI (n = 162) had the highest mean wait time of 8.28 days for power WCs. The second highest wait time was 6.29 days (SD 6.6) for manual ultralight rigid WCs (n = 34).Conclusion: Inpatient fleet WC delivery is critical to patients with SCI. Variation occurs by WC type requested and by the level of injury. Gaps exist in providing appropriate WCs in facility timeframe guidelines by the level of urgency that is within 24 h for high, 3-5 days for medium, and 5-7 days for low.

Social goals in girls transitioning to adolescence: associations with psychopathology and brain network connectivity.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

A preliminary investigation into cortical structural alterations in adolescents with nonsuicidal self-injury.

The structural neural correlates underlying youth nonsuicidal self-injury (NSSI) warrant further exploration. Few studies have explored the association between NSSI and brain structure in adolescence, and no studies have investigated differences in the relation between age and brain structure in youth with NSSI. This preliminary investigation examined associations between NSSI history, age, and cortical structure using magnetic resonance imaging in adolescent girls (N=100, Mage=13.4 years) at increased risk for psychopathology. We conducted whole-brain analyses to investigate the associations between age and cortical structure, NSSI history and cortical structure, and NSSI history as a moderator of the association between age and cortical structure. Results suggested that age was associated with less cortical thickness and surface area in the left and right prefrontal, temporal, and parietal cortex. NSSI history was associated with less left insula and left inferior parietal cortex cortical surface area. Among adolescents with NSSI history, older age predicted greater left inferior parietal cortex surface area and was not associated with left precentral cortex surface area. Among adolescents without NSSI history, older age predicted smaller surface areas as expected with the typical trajectory of neurodevelopment. Overall, our results suggest differences in cortical surface area development in adolescents with NSSI history.