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Introduction: Unprovoked seizures are common events in children, occurring as single episodes or recurring, as seen in epilepsy. The First Unprovoked Seizure (FUS) poses diagnostic challenges and raises concerns about aetiology, the initiation of anti-seizure medication and prognosis. The roles of Electroencephalogram (EEG) and neuroimaging in the diagnosis and management of FUS are debated. While EEGs play a crucial role in identifying seizure onset and epilepsy syndromes, neuroimaging aids in diagnosing underlying pathologies. Despite recommendations for routine EEGs in evaluating FUS, the role of neuroimaging remains less defined. Aim: To characterise the clinical profile of children presenting with FUS and investigate the relationship between clinical features, EEG findings and neuroimaging findings. Additionally, it explores the aetiology of FUS based on patterns of neuroradiological abnormalities and EEG changes. Materials and Methods: A cross-sectional study was conducted from April 2021 to July 2022 in the Paediatric Intensive Care Unit (PICU) and Paediatric Ward at Government TD Medical College, Alappuzha, Kerala, India. A total of 72 children aged beyond the neonatal period up to 12 years who were admitted with FUS at a tertiary care centre over an 18-month period were included in the study. Clinical data were recorded and standard techniques were used to perform EEGs and Magnetic Resonance Imaging (MRI) on all subjects. Results: The minimum age of participants in the study was two months, with a median age of 3.9 years. Among the 72 participants, most were in the infantile age group, with 23 (31.94%) falling into this category. The most frequently observed seizure type was generalised onset, with 47 (65.28%) cases. EEG irregularities were noted in 25 (34.72%) subjects, while 21 (29.16%) showed MRI abnormalities. Most frequent EEG abnormalities included generalised spike-and-wave discharges in 7 (28%) cases and modified hypsarrhythmia in 6 (24%) cases. The MRI scans revealed ischaemic changes and cerebral dysgenesis, each occurring in 7 out of 21 cases. A considerable proportion of children with abnormal EEGs had abnormal neuroimaging findings. Conclusion: The study recommends that both EEG and MRI should be included as part of the routine evaluation for children presenting with FUS. In cases with abnormalities in EEG, the detection rate of abnormalities through MRI was statistically significant. Additionally, MRI should be performed even when the EEG results are normal.

Plant growth regulators (PGRs) control signaling networks and developmental processes involved in plant responses to various biotic and abiotic stresses, making it crucial to study PGRs in vitro . The protocol for micropropagation of Solanum lycopersicum L., following callus induction and regeneration through explants such as internodal segments, leaves, and nodal segments, was established during the present study. Explants were inoculated on Murashige and Skoog (MS) medium supplemented with different plant growth regulators like BA (6-benzylaminopurine), 2,4-D (2,4-dichlorophenoxyacetic acid), BA + 2,4-D, IAA (Indoleacetic acid), IBA (Indolebutyric acid), and NAA (Naphthaleneacetic acid). It was observed that among all explants, the nodal segment showed maximum callus induction (83.33%) and multiplication (86.67%) at 0.25 mg/l of 2,4-D; the highest shoot number (3.33) at 0.5 mg/l of IAA + 0.5 mg/l of BA; the greatest shoot length (7.57 cm) at 0.75 mg/l of BA; root induction (80.95%), root number (21.88), and root length (10.62 cm) at 1 mg/l of IAA. Additionally, the maximum fresh weight (2.448 g) was observed at 0.5 mg/l of BA, while the highest dry weight (0.172 g) and dry matter content (14.25%) were noted at 1 mg/l of BA + 1 mg/l of 2,4-D for the internodal segment. Results of the present study revealed that among different explants, the best response was given by nodal segments, followed by internodal segments. Among the different PGRs, 2,4-D resulted in the highest callus induction and multiplication percentage.

Background and Aims: The lack of a dedicated pain service catering to the postsurgical period has resulted in the origination of the pain–period gap. This has led to a resurgence of transitional pain service (TPS). Our objective was to evaluate the feasibility of TPS in pain practice among postsurgical cancer patients and its prevention of persistent postsurgical pain (PPSP), culminating in chronic pain catastrophising. Methods: The protocol for this meta-analysis was registered in the International Prospective Register of Systematic Reviews (ID: CRD42023407190). This systematic review included articles involving all adult cancer patients undergoing cancer-related surgery experiencing pain, involving pharmacological, non-pharmacological and interventional pain modalities after an initial systematic pain assessment by pain care providers across diverse clinical specialities, targeting multimodal integrative pain management. Meta-analysis with meta-regression was conducted to analyse the feasibility of TPS with individual subgroup analysis and its relation to pain-related patient outcomes. Results: Three hundred seventy-four articles were evaluated, of which 14 manuscripts were included in the meta-analysis. The lack of randomised controlled trials evaluating the efficacy of TPS in preventing PPSP and pain catastrophising led to the analysis of its feasibility by meta-regression. The estimate among study variances τ2 was determined and carried out along with multivariate subgroup analysis. A regression coefficient was attained to establish the correlation between the feasibility of TPS and its patient outcome measures and opioid-sparing. Conclusion: TPS interventions carried out by multidisciplinary teams incorporating bio-physical-psychological pain interventions have resulted in its successful implementation with improved pain-related patient outcomes mitigating the occurrence of PPSP.

Abstract Tuberculosis (TB) is the top cause of death from a single infectious pathogen after COVID-19. Despite molecular diagnostic advances, two-thirds of the 10 million annual TB cases are still diagnosed using direct smear microscopy which has ~50% sensitivity. To increase the analytical performance of smear microscopy, we developed and characterized a novel polymer (Polydiallyldimethylammonium chloride [PDADMAC]) engraftment on inexpensive polystyrene (PS) specifically functionalized for mycobacterial capture. Engraftment is achieved via UV photopolymerization of DADMAC monomer on plasma-activated PS. The platform was tested on sputum from presumptive TB cases in Kampala, Uganda (n = 50), with an increased overall sensitivity of 81.8% (27/33) vs. fluorescent smear microscopy 57% (19/33) compared to a molecular (Cepheid GeneXpert MTB/RIF) gold standard. Frugal smear diagnostic innovation that is rapid and does not require dedicated instrumentation may offer an important solution to bridge the TB diagnostic gap. Graphical Abstract

Abstract Cervical cancer is a common malignant tumor of the female reproductive system and the leading cause of death among women worldwide. The survival prediction method can be used to effectively analyze the time to event, which is essential in any clinical study. This study aims to bridge the gap between traditional statistical methods and machine learning in survival analysis by revealing which techniques are most effective in predicting survival, with a particular emphasis on improving prediction accuracy and identifying key risk factors for cervical cancer. Women with cervical cancer diagnosed between 2013 and 2015 were included in our study using data from the Surveillance, Epidemiology, and End Results (SEER) database. Using this dataset, the study assesses the performance of Weibull, Cox proportional hazards models, and Random Survival Forests in terms of predictive accuracy and risk factor identification. The findings reveal that machine learning models, particularly Random Survival Forests (RSF), outperform traditional statistical methods in both predictive accuracy and the discernment of crucial prognostic factors, underscoring the advantages of machine learning in handling complex survival data. However, for a survival dataset with a small number of predictors, statistical models should be used first. The study finds that RSF models enhance survival analysis with more accurate predictions and insights into survival risk factors but highlights the need for larger datasets and further research on model interpretability and clinical applicability.

Abstract Aim The current study emphasizes the impact of adverse drug reactions (ADRs) and Drug-Related Problems (DRPs) caused by supportive care medications administered with chemotherapy. Method This is a longitudinal observational study carried out at the Ramaiah Medical College Hospital in Bengaluru, Karnataka, India, at the Department of Oncology. The data was recorded using a specifically created data collecting form. Based on the PCNE (Pharmaceutical Care Network Europe), DRPs are identified. The WHO probability scale, Modified Hartwig and Siegel for ADR severity assessment, Naranjo's algorithm for causality assessment, Rawlins and Thompson for predictability assessment, and Modified Shumock and Thornton for preventability assessment were all utilized. The OncPal guideline was considered in terms of the precision of supportive care medications regarding the reduction of ADRs in cancer patients. Result We enrolled 302 patients,166 (55%) female and 136 (45%) male (SD 14.378) (mean 49.97), patients with one comorbidity 59(19.6%) and multimorbidity (two or more) 45(14.9%), the DRPs identified were found to be 153 (50.6%); only P2 (safeties of drug therapy PCNE) were considered in this study. ADRs which are identified 175(57.9%) contributed/caused by the supportive care medications. WHO probability scale: 97 (32.1%) possible and 60 (19.9%) unlikely; Naranjo’s algorithm: 97 (32.1%) unlikely and 69 (22.8%) possible; ADR severity assessment scale (Modified Hartwig and Siegel): 95 (31.5%) mild and 63 (20.9%) moderates; Rawlins and Thompson for determining predictability of an ADR: 33 (10.9%) predictable and 137 (45.5%) non-predictable; and Modified Shumock and Thornton for determining preventability of an ADR: 81 (26.8%) probably preventable and 90 (29.8%) non-preventable. The statistical comparison through preforming t-test and measuring Chi-Square between group with ADRs and without ADRs shows in some variables, significantly (Alcohol consumption status, P = .019) and Easter Cooperative Oncology Group (ECOG) performance status P

Abstract POT1 variants have been identified in familial melanoma (FM) as well as a number of other germline and somatic malignancies. The functional validation of variants identified from the screening of patients with melanoma gene susceptibility panels is key to understanding the clinical significance of identified variants. Here we report a novel, likely pathogenic POT1 missense variant (p.G95V) in FM and investigate its functional impact. We demonstrate loss of function owing to the inability of the mutant POT1 protein to bind telomeric DNA compared to its wild‐type counterpart. This study provides important functional validation of a novel POT1 variant in FM.

Purpose: To present the outcomes of the mask-associated dry eyes (MADE) survey in an Indian scenario. Methods: An online survey was conducted amongst general population from May to July 2021 to assess the burden of dry eyes and MADE. To summarize the findings, descriptive statistics were employed, and statistical significance was determined between various mask practices and dry eye symptoms. A P value of

The majority of patients with solid tumors undergo a curative resection of their tumor burden. However, the reported rate of postoperative complications varies widely, ranging from 10% to 70%. This narrative review aims to determine the impact of postoperative complications on recurrence and overall survival rates following elective cancer surgeries, thereby providing valuable insights into perioperative cancer care. A systematic electronic search of published studies and meta-analyses from January 2000 to August 2023 was conducted to examine the effect of postoperative complications on long-term survival after cancer surgeries. This comprehensive search identified fifty-one eligible studies and nine meta-analyses for review. Recurrence-free survival (RFS) and overall survival (OS) rates were extracted from the selected studies. Additionally, other oncological outcomes, such as recurrence and cancer-specific survival rates, were noted when RFS and OS were not reported as primary outcomes. Pooled hazard ratios and 95% confidence intervals were recorded from the meta-analyses, ensuring the robustness of the data. The analysis revealed that long-term cancer outcomes progressively worsen, from patients with no postoperative complications to those with minor postoperative complications (Clavien–Dindo grade ≤ II) and further to those with major postoperative complications (Clavien–Dindo grade III–IV), irrespective of cancer type. This study underscores the detrimental effect of postoperative complications on long-term oncological outcomes, particularly after thoracoabdominal surgeries. Importantly, we found a significant gap in the data regarding postoperative complications in surface and soft tissue surgical procedures, highlighting the need for further research in this area.

This study aimed to investigate the physiological, perceptual, and biomechanical differences between male and female soldiers across several military-relevant load and walking speed combinations. Eleven female and twelve male soldiers completed twelve 12 min walking trials at varying speeds (3.5 km·h−1, 5.5 km·h−1, 6.5 km·h−1) and with varying external loads (7.2 kg, 23.2 kg, 35.2 kg). Physiological (indirect calorimetry, heart rate), perceptual (perceived exertion), and biomechanical (spatiotemporal, kinematic, kinetic) outcomes were measured throughout each trial. Females had a lower aerobic capacity and lower body strength than males, which resulted in them working at a greater exercise intensity (%VO2peak and heart rate) but with a lower oxygen pulse. Females demonstrated higher breathing frequency and perceived exertion with specific loads. At selected loads and speeds, frontal and sagittal pelvis, hip, and knee motions and forces were greater for females. Females consistently displayed greater relative stride length and step width. In conclusion, this study demonstrates the importance of tailored interventions, periodisation, and nutritional strategies for female military personnel, given their higher relative work rate and increased injury risk during load carriage tasks. Understanding these differences is crucial for preparing female soldiers for the physical demands of military service.

Background: Neonatal electrocardiogram (ECG) screening can potentially identify congenital long QT syndrome and other heart diseases. Early identification is likely to reduce mortality. A barrier is the difficulty in obtaining a 12-lead ECG in an infant. We aimed to assess the feasibility of using a single lead ECG recorded with a handheld device (Eko DUO) in neonates. Methods: This cross-sectional study included neonates in the first 3 days of life. We recorded a single-lead ECG using the Eko DUO. Time from the beginning of recording until a satisfactory recording was measured with a stopwatch and reported as mean and standard deviation. We reported the ratio of interpretable recordings and the proportion of those with any abnormalities. Results: The mean time for recording was 198.1 ± 94.7 s. The total number of interpretable recordings was 63% (n = 63). Of the interpretable recordings, one neonate was found to have tachycardia (1.6%). Conclusions: Neonatal ECG screening using Eko DUO is feasible. However, the fidelity of the recorded ECG is suboptimal. While most of the ECGs were interpretable for rate and rhythm, QT interval measurement was not possible in most neonates.

Introduction:Gunas act as tools for predicting or assessing the karma. Understanding the guna will help in the application of dravyas in treatment. Certain experimental techniques are being used as parameters for the evaluation of Gurvadi gunas. Ushna guna is having a prominent action on the Jatharagni and it helps in Pachana. The present study is an attempt to find out the possibility of employing carbohydrate estimation by hydrolysis in assessing Ushna-Sheeta guna. This was done by determining the effect of selected Ushna-Sheeta guna drugs on hydrolysis of Mudga and ultimately on its carbohydrate content.Methods:Estimation of carbohydrates of Mudga, Maricha, and Usheera was done by Anthrone method. Then Mudga was subjected to hydrolysis in the presence of Maricha in one sample and Usheera in another sample. These samples were subjected to estimation of carbohydrates.Results:The mean carbohydrate content in Mudga alone was 107.69 mg/100 mg. After hydrolysis of Mudga in the presence of Maricha (8:2), the mean carbohydrate content of sample increased to 114.65 mg/100 mg of sample. Similarly, after hydrolysis of Mudga in the presence of Usheera (8:2), the mean carbohydrate content of sample increased to 110.7 mg/100 mg of sample.Conclusion:Percentage of conversion is 1.9% in Maricha group and is 17.81% in Usheera group, which is against the Ayurveda concept of Ushna guna aiding in Pachana. The ushna and sheeta gunas might come into action in the presence of digestive enzymes and this might again depend on other constituents of drugs.

Sustainable soil fertility management is crucial for enhancing productivity in coconut plantations. This study investigated the synergistic effects of king coconut husk (KCH) ash, biochar, and chemical fertilizers on soil properties in a coconut plantation over a short period (4 months). Six treatments were applied: control, chemical fertilizers alone (F), fertilizers with ash (FA), fertilizers with biochar (FB), fertilizers with both ash and biochar (FAB), and fertilizers with half ash and biochar (FA1/2B). Strongly alkaline KCH ash contained significantly higher total and available potassium content levels than mildly alkaline biochar. Data indicated that KCH ash significantly enhanced soil available potassium, electrical conductivity, and organic carbon content compared to the control and F treatments over a short-term period. Even though biochar application demonstrated initial improvements in soil moisture content, a longer study duration may be required to evaluate its influence on other soil parameters comprehensively. Highlighting the synergistic benefits of KCH ash and biochar, FA1/2B treatment exhibited the highest combined index score based on physical, biological, and chemical soil indicators, suggesting its potential for optimizing agricultural outcomes. It emerged as the most promising approach, underscoring the value of exploring sustainable soil amendments derived from agricultural waste streams to promote soil fertility and sustainable coconut production.

Introduction: While placing the Proseal-laryngeal Mask Airway (PLMA) using the digital technique, there may be failed insertion or inadequate ventilation. Therefore, a placement technique using the Gum Elastic Bougie (GEB)-aided placement was employed. Aim: To compare the clinical efficacy of Proseal Laryngeal Mask Airway (PLMA) insertion by two different techniques viz. Digital and Gum elastic bougie-aided, in mastoid surgery in adult patients done under General Anaesthesia. Materials and Methods: In this randomised clinical study conducted at the Department of Anaesthesiology, R.G. Kar Medical College, Kolkata, West Bengal, India from November 2016 to December 2022. A total of 88 patients of American Society of Anaesthesiologists (ASA) class I and II of either sex undergoing mastoid surgery using the PLMA as an airway management device were allocated to Digital (Group D) and gum elastic Bougie (Group B) techniques. Parameters studied included the percentage of successful insertion of PLMA on the first attempt, number of attempts required and time taken for successful insertion of PLMA and postoperative complications if any. The t-test was used to compare the groups regarding PLMA insertion time, while categorical data such as airway trauma was compared using Chi-square test or Fischer’s-exact test (whichever applicable). Results: In the present study 88 patients were included, with 44 patients in each of the two groups. The difference in Mallampati scoring of both groups was statistically insignificant. In the present study 68.18% patients in Gum elastic bougie group and 70.45% patients in Digital group were of ASA Grade I, showing no statistical significance between these two groups regarding ASA status. In Group B (GEB), PLMA was successfully inserted in 95.45% of cases on the first attempt, and in group D (digital) the corresponding figure was 77.27% and 22.72% of cases required a 2nd attempt, this difference was statistically significant (p-value

Abstract Background Like its parent base 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) is a direct epigenetic modification of cytosines in the context of CpG dinucleotides. 5hmC is the most abundant oxidized form of 5mC, generated through the action of TET dioxygenases at gene bodies of actively-transcribed genes and at active or lineage-specific enhancers. Although such enrichments are reported for 5hmC, to date, predictive models of gene expression state or putative regulatory regions for genes using 5hmC have not been developed. Results Here, by using only 5hmC enrichment in genic regions and their vicinity, we develop neural network models that predict gene expression state across 49 cell types. We show that our deep neural network models distinguish high vs low expression state utilizing only 5hmC levels and these predictive models generalize to unseen cell types. Further, in order to leverage 5hmC signal in distal enhancers for expression prediction, we employ an Activity-by-Contact model and also develop a graph convolutional neural network model with both utilizing Hi-C data and 5hmC enrichment to prioritize enhancer-promoter links. These approaches identify known and novel putative enhancers for key genes in multiple immune cell subsets. Conclusions Our work highlights the importance of 5hmC in gene regulation through proximal and distal mechanisms and provides a framework to link it to genome function. With the recent advances in 6-letter DNA sequencing by short and long-read techniques, profiling of 5mC and 5hmC may be done routinely in the near future, hence, providing a broad range of applications for the methods developed here.

Abstract Phase separation and percolation contribute to phase transitions of multivalent macromolecules. Contributions of percolation are evident through the viscoelasticity of condensates and through the formation of heterogeneous distributions of nano- and mesoscale pre-percolation clusters in sub-saturated solutions. Here, we show that clusters formed in sub-saturated solutions of FET (FUS-EWSR1-TAF15) proteins are affected differently by glutamate versus chloride. These differences on the nanoscale, gleaned using a suite of methods deployed across a wide range of protein concentrations, are prevalent and can be unmasked even though the driving forces for phase separation remain unchanged in glutamate versus chloride. Strikingly, differences in anion-mediated interactions that drive clustering saturate on the micron-scale. Beyond this length scale the system separates into coexisting phases. Overall, we find that sequence-encoded interactions, mediated by solution components, make synergistic and distinct contributions to the formation of pre-percolation clusters in sub-saturated solutions, and to the driving forces for phase separation.

We previously showed that the anticancer drug imatinib mesylate (IMT, trade name: Gleevec) and a chemically distinct compound, DV2-103 (a kinase-inactive derivative of the potent Abl and Src kinase inhibitor, PD173955) lower Aβ levels at low micromolar concentrations primarily through a lysosome-dependent mechanism that renders APP less susceptible to proteolysis by BACE1 without directly inhibiting BACE1 enzymatic activity, or broadly inhibiting the processing of other BACE1 substrates. Additionally, IMT indirectly inhibits γ-secretase and stimulates autophagy, and thus may decrease Aβ levels through multiple pathways. In two recent studies we demonstrated similar effects on APP metabolism caused by derivatives of IMT and DV2-103. In the present study, we synthesized and tested radically altered IMT isomers (IMTi’s) that possess medium structural similarity to IMT. Independent of structural similarity, these isomers manifest widely differing potencies in altering APP metabolism. These will enable us to choose the most potent isomers for further derivatization.

Abstract Vapor phase infiltration (VPI) has emerged as a promising tool for fabrication of novel hybrid materials. In the field of polymeric gas separation membranes, a beneficial impact on stability and membrane performance is known for several polymers with differing functional groups. This study for the first time investigates VPI of trimethylaluminum (TMA) into poly(1‐trimethylsilyl‐1‐propyne) (PTMSP), featuring a carbon–carbon double bond as functional group. Saturation of the precursor inside the polymer is already attained after 60 s infiltration time leading to significant densification of the material. Depth profiling proves accumulation of aluminum in the polymer itself, but a significantly increased accumulation is visible in the gradient layer between polymer and SiO2 substrate. A reaction pathway is proposed and supplemented by density‐functional theory (DFT) calculations. Infrared spectra derived from both experiments and simulation support the presented reaction pathway. In terms of permeance, a favorable impact on selectivity is observed for infiltration times up to 1 s. Longer infiltration times yield greatly reduced permeance values close or even below the detection limit of the measurement device. The present results of this study set a strong basis for the application of VPI on polymers for gas‐barrier and membrane applications in the future.

Introduction: Depression is a major public health concern among the elderly, affecting their quality of life and overall well-being. Despite the increasing elderly population in Nepal, data on the prevalence of depression in rural areas is limited. Therefore, this study aims to assess the prevalence of depression among the geriatric population. Methods: A cross-sectional study was conducted among individuals aged 60 years and above in three randomly selected wards of Shivapuri Rural Municipality. Respondents were selected using consecutive sampling. The Nepali version of the Geriatric Depression Scale (GDS-15) was administered through face-to-face interviews. Ethical approval was obtained from the Institutional Review Committee (Reference number 080/81-437). Descriptive analysis was conducted for categorical variables using the Statistical Package for the Social Sciences (SPSS). Results: The overall prevalence of geriatric depression was 115 (28.75%; 95% CI: 24.36%-33.46%), with a mean depression score of 3.54 ± 3.17. Among those with depression, majority reported mild depression 79 (68.70%) reported mild depression, 79 (31.22%) were male, 88 (30.66%) were under 75 years of age, 46 (35.66%) self-rated their health as not good, 16 (32.66%) had COPD and 33 (30%) were hypertensive elderly. Conclusions: About one third of the elderly reported of having depression and more than 50% had mild depression. The depresson was more in age group less than 75 years, male, married and in nuclear family.

There is a well-documented racial and ethnic diversity crisis in Geography, Earth and Environmental Sciences (GEES) subjects in the Global North that leads to inequities in who does environmental research. The Equator project set out to increase participation and retention of UK-domiciled Black, Asian and minority ethnic students in GEES research by developing evidence-based, ring-fenced, fully remunerated interventions. These interventions were co-created with and informed by the voices of students and professionals within the GEES community, following a Theory of Change-based, action research approach. The Equator Research School brought together 30 Black, Asian and minority ethnic students in GEES, and 12 academics, professionals and mentors, from across the UK for a 5-day residential workshop in April 2022. The Research School was designed to facilitate network-building, improve awareness of research careers, enhance confidence in continuing in research, and strengthen a sense of belonging in GEES research for participants. The Equator Mentoring Network, which took place from January to May 2022, facilitated networking between 10 Black, Asian and minority ethnic student mentees and 20 academic and industry mentors involved in GEES subject areas. The overall goal of the Mentoring Network was to increase retention of Black, Asian and minority ethnic students into postgraduate research and to improve their overall experience. Evaluation of these interventions took the form of surveys to capture thoughts and reflections before, during and after interventions. Participants in both interventions provided very positive feedback; the majority of those involved felt a stronger sense of belonging and inclusion in GEES research and were more likely to consider a research career after taking part. The evaluation process showed unequivocally that the ring-fenced, discipline-specific, fully funded nature of the interventions was a critical factor in participant involvement. The work led to the development of recommendations for creating successful interventions for improving participation and retention in research, as well as templates for future, related EDI activities.

The oxidative coupling of methane (OCM) to produce ethane and ethylene (C2 compounds) as platform chemicals involves complex chemistry with reactions both in the gas phase and on the catalyst surface, resulting in a distribution of products at the expense of C2 selectivity. This work uses experimental data from a variety of mixed metal oxides on supports at different reaction conditions (temperature, contact time, and reactant flow rates) to train a random forest regressor that predicts methane conversion and C2 selectivity (key performance indicators (KPIs)). The kinetically validated random forest models are deployed to locate optimal conditions that maximize C2 yield for each of the catalysts. Investigating the regressor interpretability via feature importance reveals that the choice of metals and support are crucial to C2 selectivity predictions in addition to the reaction conditions, while the predictions of methane conversion are largely governed by the reaction conditions. The machine learning (ML) regressor is used as a kinetic surrogate to find a locus of optimal reaction conditions that maximize both selectivity-conversion for each of the catalysts via a multi-objective optimization routine. The maximum C2 yields for catalysts are projected to be improved by 15% on average. Analyzing the catalysts with respect to a popular OCM catalyst, Mn-Na2WO4/SiO2, using the optimal locus eliminates variability in the process conditions to reveal distinct patterns based on intrinsic properties of metals and supports. Further, the decision space with catalyst descriptors and reaction conditions is optimized for high C2 yields using the ML surrogate, in a static multi-objective optimization routine, and an adaptive Bayesian routine, where the latter was found to have a wider field focus in proposing catalyst formulations and reaction conditions. Transition metal oxides on a variety of supports were proposed but not their lanthanide oxide counterparts. The framework has the potential to lend itself to materials acceleration platforms where it is crucial to consider multi-scale phenomena that impact downstream KPIs.

Background: This study compares seed germination and seedling growth parameters of native Senegalia catechu with its closely related invasive Leucaena leucocephala in Nepal. For the comparison of seed germination percentage (GP), mean germination time (MGT), and Timson’s index (TI), the seeds of both species were incubated under different light (photoperiod and dark), tiperatures (30/20ºC and 25/15ºC) and water stress conditions (−0.1, −0.25, −0.5, −0.75, and −1 MPa). The seedling iergence from different soil depths was also evaluated. The relative growth rate (RGR), root mass fraction (RMF), sti mass fraction, leaf mass fraction (LMF), and root-to-shoot ratio (RSR) of seedlings were also measured. Results: The seed length and mass of invasive L. leucocephala were higher than that of native S. catechu. The GP of S. catechu was higher at high tiperature and photoperiod comparing to L. leucocephala. There was no difference in GP between two species under other light and tiperature conditions. The MGT of S. catechu was shorter than that of L. leucocephala at both tiperatures. Senegalia catechu exhibited higher TI than L. leucocephala, particularly at high tiperatures. Water stress above −0.5 MPa reduced the GP and TI of both species and it was more pronounced in S. catechu than L. leucocephala. The seedling iergence percentage of L. leucocephala was higher than that of S. catechu. Both species exhibited comparable RGR and biomass allocations (RMF, LMF, and RSR). However, L. leucocephala had always greater values of shoot height, root length, leaf number and seedling biomass compared to S. catechu. Conclusions: Larger seeds may not always lead to higher seed GP. Some, but not all, seed germination and seedling growth traits can be useful to characterize invasive alien plant species. Invasiveness of L. leucocephala could be attributed to relatively high tolerance of seed germination to water stress, capacity to germinate from deeper soil, and larger seedling size compared to the confamilial native species.

The demographics of environmental and Earth scientists are not representative of the UK’s multicultural society. We sought to widen diversity and engage equitably through two related engaged research projects, “Walking the Walk” and “Landscape Stories.” This paper offers a critically reflexive account, based on the methodology of duoethnography, of how we co-constructed a “third space” with and for minoritized community groups and environmental scientists. We sought to create the conditions for inclusive leadership informed by connectedness, respect, humility and intentionality. We argue that for environmental and Earth science research to be more equitable and inclusive, members of project teams should be engaged and more representative of wider society. Following this, collective work to create third spaces requires: respect for diversity and different forms of expertise, knowledge starting points, power dynamics and esteem; a willingness to make connections across disciplines and sub-cultures, actively listening and (un)learning from different (knowledge) cultures; and a commitment to be respectful of hidden and manifest difference, exploring purpose and gaps in knowledge in more holistic ways.

Targeted therapies are the mainstay of systemic therapies for patients with advanced, unresectable, or metastatic hepatocellular carcinoma. Several therapeutic targets, such as c-Met, TGF-β, and FGFR, have been evaluated in the past, though results from these clinical studies failed to show clinical benefit. However, these remain important targets for the future with novel targeted agents and strategies. The Wnt/β-catenin signaling pathway, c-Myc oncogene, GPC3, PPT1 are exciting novel targets, among others, currently undergoing evaluation. Through this review, we aim to provide an overview of previously evaluated and potentially novel therapeutic targets and explore their continued relevance in ongoing and future studies for HCC.

IntroductionDietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.ObjectiveTo investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.MethodsThis study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.ResultsOver 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.ConclusionEncouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

The exposure of human beings to various respiratory diseases has sparked an interest among scientists to propose and promote inhalable nanoparticle-based pharmaceutical products. This new drug delivery system will be an effective and prompt therapy for next-generation respiratory therapeutics. There are many available formulations on account of the treatments for lung diseases, i.e., oral, injectable, aerosol, nebulizer-based, etc. But, due to extended distribution and elimination, repeated intake, and complex systems of application, these treatments create overload on patients along with other expenses of daily life. Amid these treatments, inhalable nanoparticle-based dry powder formulations are considered superior owing to their simplicity, convenience of use, and long-term stability. This review aims to formulate an inhalable nanoparticle dry powder formulation to attain confined distribution of the remedy to the respiratory system. Dry powder formulations based on inhalable nanoparticles provide a novel and cutting-edge method of treating lung conditions. This novel drug delivery system is an improved treatment for lung disorders in terms of its efficacy and reduced dose requirement. Subsequently, the availability of this formulation will be an alternative option for patients to improve treatment compliance and, foremost, therapeutic outcomes in different lung ailments. The salient features of dry formulations that illustrate their uniqueness are deep penetration to lung tissues, enhanced deposition in lung regions, improved solubility, elevated bioavailability, targeted drug delivery, stability at storage, convenient to use, versatile and customizable formulation. This novel inhalable formulation is based on finely dried nanoparticles or freeze-dried particles. This formulation will contain an excessive amount of dried nanoparticles, and if it is combined with a beneficial tool, i.e., a spray, pump, or puffer, it will be a pleasant way to apply drugs directly to the lungs.

Summary: Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA sequencing revealed that >80% of cells in thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.

Biomaterials that can be reversibly stiffened and shaped could be useful in broad biomedical applications where form-fitting scaffolds are needed. Here we investigate the combination of strong non-linear elasticity in biopolymer networks with the reconfigurability of packed hydrogel particles within a composite biomaterial. By packing microgels into collagen-1 networks and characterizing their linear and non-linear material properties, we empirically determine a scaling relationship that describes the synergistic dependence of the material's linear elastic shear modulus on the concentration of both components. We perform high-strain rheological tests and find that the materials strain stiffen and also exhibit a form of programmability, where no applied stress is required to maintain stiffened states of deformation after large strains are applied. We demonstrate that this non-linear rheological behavior can be used to shape samples that do not spontaneously relax large-scale bends, holding their deformed shapes for days. Detailed analysis of the frequency-dependent rheology reveals an unexpected connection to the rheology of living cells, where models of soft glasses capture their low-frequency behaviors and polymer elasticity models capture their high-frequency behaviors.

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003–2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15–48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien–Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range – 13.25–47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]–83%–97%) and the overall survival (OS) rate was 90% (95% CI–80%–95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

Background: Development of esophageal varices is one of the major complications of liver cirrhosis, and endoscopy is used to see the presence, grading, and long-term monitoring of esophageal varices which is an invasive and unpleasant procedure. There is no adequate data available showing noninvasive methods can be used for the same. Methods: Seventy patients with liver cirrhosis participated in the study. Factors like portal vein diameter, spleen size, platelet count, serum bilirubin, Child-Pugh score, prothrombin time (PT), and PT INR were observed and correlated endoscopically with the presence and grading of esophageal varices in all patients. Results: The platelet count, portal vein diameter, serum bilirubin, spleen bipolar diameter, and PT had statistically significant correlations with the presence of varices. Among them, platelet count, portal vein diameter, and serum bilirubin also had statistically significant correlations with the grading of varices. Monitoring of these noninvasive parameters can help in monitoring variceal growth. Conclusions: Noninvasive parameters can be used effectively to predict the presence and grading of esophageal varices and at the same time keep the rate of undiagnosed varices acceptably low. By using noninvasive parameters, patients can be benefited by decreasing the requirement of repeated endoscopic evaluation which is an unpleasant procedure and availability is also limited.

Abstract Background Klebsiella pneumoniae infections have become a major cause of hospital acquired infection worldwide with the increased rate of acquisition of resistance to antibiotics. Carbapenem resistance mainly among Gram negative is an ongoing problem which causes serious outbreaks dramatically limiting treatment options. This prospective cross-sectional study was designed to detect bla KPC gene from carbapenem resistant K. pneumoniae. Materials and Methods A totally of 1118 different clinical specimens were screened and confirmed for KPC producing K. pneumoniae phenotypically using Meropenem (10 μg) disc. The bla KPC gene was amplified from the isolates of K. pneumoniae to detect the presence of this gene. Result Of the total samples processed, 18.6% (n = 36) were K. pneumoniae and among 36 K. pneumoniae, 61.1% (n = 22/36) were meropenem resistant. This study demonstrated the higher level of MDR 91.7% (n = 33) and KPC production 47.2% (n = 17) among K. pneumoniae isolates. The bla KPC gene was detected in 8.3% (n = 3) of meropenem resistant isolates. Conclusion Since the study demonstrates the higher level of MDR and KPC producing K. pneumoniae isolates that has challenged the use of antimicrobial agents, continuous microbiology, and molecular surveillance to assist early detection and minimize the further dissemination of bla KPC should be initiated. We anticipate that the findings of this study will be useful in understanding the prevalence of KPC-producing K. pneumoniae in Nepal.

Abstract DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial species, driving the hypothesis that a physical linker may tether them together. However, replisome splitting has also been reported in many of the same species, leaving the principles behind replisome organization a long-standing puzzle. Here, by tracking the replisome β-clamp subunit in live Caulobacter crescentus, we find that rapid DNA segregation can give rise to a second focus which resembles a replisome, but does not replicate DNA. Sister replisomes can remain colocalized, or split apart to travel along DNA separately upon disruption of chromosome inter-arm alignment. Furthermore, chromosome arm-specific replication-transcription conflicts differentially modify replication speed on the two arms, facilitate the decoupling of the two replisomes. With these observations, we conclude that the dynamic chromosome organization flexibly shapes the organization of sister replisomes, and we outline principles which can help to reconcile previously conflicting models of replisome architecture.

Abstract Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These ‘persister’ cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.

Abstract Background Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. Objectives This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. Methods Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5–17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. Results We validated a high-throughput methodology using LC–MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12–0.29 µmol/L), CerC18:0 (0.019–0.067 µmol/L), CerC22:0 (0.102–0.525 µmol/L), CerC24:0 (0.65–1.54 µmol/L) and CerC24:1 (0.212–0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure and, hence, is distressing for awake patients, requiring an adequate level of anesthesia. Recent advancements have encouraged the use of monitored anesthesia care, that allows the patient to tolerate unpleasant experiences during procedures while maintaining cardio-respiratory function. Usually, propofol-based anesthesia is given in ERCP. The main aim of this study is to compare the effect of propofol alone and propofol with ketamine and dexmedetomidine on the hemodynamics during ERCP, recovery profile, and side effects (if any). Aims and Objectives: (1) To compare efficacy in terms of hemodynamic stability and desaturation events. (2) Recovery and quality of recovery. (3) Pain score. (4) Incidence of post-operative nausea and vomiting. Materials and Methods: This is a comparative double-blinded study. Adult patients from the age group of 18–70 years belonging to the American Society of Anesthesiologists (ASA-I) and ASA-II who had undergone ERCP under total intravenous anesthesia were taken and randomly assigned to either of the two groups. Both groups received 0.01 mg/kg glycopyrrolate, 0.1 mg/kg ondansetron, 0.05 mg/kg midazolam, 50 mcg fentanyl, and 40 mg hyoscine. Group A patients received 30 mg propofol as a bolus dose and then repeated according to requirements. Group B patients received 0.5 mcg/kg dexmedetomidine as a loading dose and 0.3 mcg/kg/h as a maintenance infusion dose. 30 mg propofol was given before negotiating scope and then 1 mL (1:1) mixture of propofol and ketamine was repeated according to requirements. Total propofol consumption, hemodynamics, quality of recovery, and side effects (if any) were recorded at regular intervals. Results: The study showed significant cases in Group A had episodes of hypotension and apneic events, whereas there were very few hemodynamic instability and almost no apneic events in Group B patients. The requirement of propofol was much higher in Group A patients. Conclusion: Dexmedetomidine when used along with propofol and ketamine in ERCP patients reduced the dose requirement of propofol and maintained hemodynamic stability without causing any apneic events.

Aims: We compared the efficacy, fidelity, acceptability, and feasibility of a creative movement (CM) intervention for children with autism spectrum disorder (ASD), delivered face-to-face (F2F) or through telehealth (TH). Methods: Fifteen children with ASD received the CM intervention F2F or through TH. Motor assessments were used to evaluate effects of F2F and TH interventions on children's motor skills, while video coding was used to assess affect, socially directed verbalization, interpersonal synchrony, and motor coordination during training. Stakeholder feedback and training fidelity data on the intervention were also collected. Results: Children in both subgroups showed similar baseline performance and training-related improvements in motor skills, positive/interested affect, socially directed verbalization, interpersonal synchrony, and dual/multilimb coordination. Parents in the TH subgroup considered the intervention feasible and acceptable; however, they reported greater effort to supervise and redirect their child's attention compared to the F2F subgroup. Trainers for the TH subgroup reported more communication difficulties, technological issues, and longer session lengths, but found greater parental involvement compared to the F2F subgroup. Conclusions: CM interventions are consistent, acceptable, feasible, and effective in improving social, behavioral-affective, and motor skills of children with ASD, regardless of the method of delivery. Clinicians should make efforts to reduce communication/technological issues and parental burden when delivering CM interventions through TH. ClinicalTrials.Gov Study ID-NCT04258254.

Abstract Numerous studies have demonstrated the correlation between human gut bacteria and host physiology, mediated primarily via nuclear receptors (NRs). Despite this body of work, the systematic identification and characterization of microbe-derived ligands that regulate NRs remain a considerable challenge. In this study, we discover a series of diindole molecules produced from commensal bacteria metabolites that act as specific agonists for the orphan constitutive androstane receptor (CAR). Using various biophysical analyses we show that their nanomolar affinities are comparable to those of synthetic CAR agonists, and that they can activate both rodent and human CAR orthologues, which established synthetic agonists cannot. We also find that the diindoles, diindolylmethane (DIM) and diindolylethane (DIE) selectively up-regulate bona fide CAR target genes in primary human hepatocytes and mouse liver without causing significant side effects. These findings provide new insights into the complex interplay between the gut microbiome and host physiology, as well as new tools for disease treatment.

Background: Secondary angle closure glaucoma (SACG) can be quite puzzling and can challenge even an experienced glaucoma surgeon. Unlike primary angle closure glaucoma, SACG can have various ocular and systemic associations. A careful review of the symptoms and past ocular and surgical history cannot be overemphasized. Some of the SACG can be refractory, requiring drainage devices. However, sometimes, all it takes is a prompt laser iridotomy. This can significantly reduce ocular morbidity and, in some situations, even blindness. Gonioscopy, often an underutilized technique, is critical in making the right diagnosis. With the advent of imaging techniques such as anterior segment optical coherence tomography and ultrasound biomicroscopy, one can easily pick up the etiology and treat early. Purpose: As many cases of SACG present acutely, it is critical that one makes a prompt diagnosis. We present here a video bouquet of illustrated examples of SACG and the steps to identify the cause by using different imaging techniques. Through this video, we aim to make the diagnosis of SACG a simpler, more streamlined, and logical process that will help in the accurate diagnosis and management. Synopsis: This video demonstrates various etiologies of secondary angle closure and methods to identify and treat the same. Highlights: Secondary angle closure can occur either with or without pupillary block. SACG with pupillary block involves mechanisms such as seclusio pupillae, aphakic/pseudophakic glaucoma, phacomorphic glaucoma, and silicon oil-induced glaucoma. In contrast, there are various other etiologies causing anterior pulling or posterior pushing mechanisms that contribute to non-pupillary block SACG. We discuss all of these, along with the imaging modalities needed to identify the same. Video link: https://youtu.be/N0bIw7Uknww.

The present study was mainly aimed to study the effect of air pollution on the morphological and anatomical characteristics of leaf of 6 common plant species viz., Bougainvillea glabra, Callistemon citrinus, Euphorbia pulcherrima, Jasminum mesnyi, Lagerstroemia indica and Nerium oleander from different location of Kathmandu Valley. Results showed that all plant species exhibited significant (p

Alpha and beta cobalt hydroxide nanostructures were synthesized by hydrothermal method and characterized using X-ray diffraction and electron microscopy. The turbostatic alpha-Co(OH)2 has large interlayer spacing compared to the beta-Co(OH)2 and is less explored in the literature. Both nanostructures were efficient in degrading methylene blue dye in the presence of visible light. Under identical conditions, the rate constant of photocatalytic dye degradation in the presence of alpha and beta cobalt hydroxide was calculated as 60.22 × 10−3 min−1 and 19.05 × 10−3 min−1, respectively, which is highest when compared to the previous reports. The superior activity of alpha-Co(OH)2 when compared to beta-Co(OH)2 is also demonstrated in this work. Additionally, a Csp value of 137 F/g and 2.4 F/g, respectively, at a current density of 1 A/g, was obtained from the GCD analysis of devices made using alpha-Co(OH)2 and beta-Co(OH)2. A higher cyclic stability and power density were observed for alpha-Co(OH)2 when compared to beta-Co(OH)2. The findings suggest that alpha and beta cobalt hydroxide nanostructures hold promise as effective catalysts for dye degradation and potential materials for high-performance supercapacitors. Further investigations into the unique properties of the relatively superior alpha-Co(OH)2 could lead to advancements in environmental remediation and energy storage technologies.

Introduction The Building on Existing Tools to Improve Cancer and Chronic Disease Prevention and Screening in Primary Care (BETTER) programme trains allied health professionals working in primary care settings to develop personalised chronic disease ‘prevention prescriptions’ with patients. However, maintenance of health behaviour changes is difficult without ongoing support. Sustainable options to enhance the BETTER programme and ensure accessibility to underserved populations are needed. We designed the BETTER Women programme, which uses a digital app to match patients with a trained peer health coach (PHC) who provides ongoing support for health behaviour change after receipt of a BETTER prevention prescription in primary care.Methods and analysis We will conduct a type 1 hybrid implementation-effectiveness patient-randomised trial. Interested women aged 40–68 years will be recruited from three large, sociodemographically distinct primary care clinics (urban, suburban and rural). Patients will be randomised 1:1 to intervention or wait-list control after receipt of their BETTER prevention prescription. We will aim to recruit 204 patients per group (408 total). Effectiveness will be assessed by the primary outcome of targeted behaviours achieved for each participant at 6 months, consisting of three cancer screening tests (cervical, breast and colorectal) and four behavioural determinants of cancer and chronic disease (diet, smoking, alcohol use and physical activity). Data will be collected through patient survey and clinical chart review, measured at 3, 6 and 12 months. Implementation outcomes will be assessed through patient surveys and interviews with patients, peer health coaches and healthcare providers. An embedded economic evaluation will examine cost per quality-adjusted life-year and per additional health behavioural targets achieved.Ethics and dissemination This study has been approved by Women’s College Hospital Research Ethics Board (REB), the Royal Victoria Regional Health Centre REB and the University of Toronto REB. All participants will provide informed consent prior to enrolment. Participation is voluntary and withdrawal will have no impact on the usual care received from their primary care provider. The results of this trial will be published in peer-reviewed journals and shared via conference presentations. Deidentified datasets will be shared on request, after publication of results.Trial registration number NCT04746859.

BackgroundLimited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS).MethodsSchool KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten–12th grade) in Kansas City, Missouri. During the 2022–2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs.ResultsFrom 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys.ConclusionRespiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures.

IntroductionCancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management.ObjectivesThe main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS).Materials and methodsA population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations.ResultsCC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS.ConclusionsUsing clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Abstract Traumatic brain injury (TBI) can have long‐lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo‐Dex were well tolerated in human and murine neural cells. Lipo‐Dex showed significant suppression of inflammatory cytokines, IL‐6 and TNF‐α, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo‐Dex were administered to young adult male and female C57BL/6 mice immediately after controlled cortical impact injury (a TBI model). Our findings demonstrate that Lipo‐Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of pro‐inflammatory cytokines, and microglial activation compared to Lipo‐treated mice in a sex‐dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano‐therapies for brain injury. These results suggest that Lipo‐Dex administration may effectively treat acute TBI.