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A novel pyrene-substituted oxacalixarene was designed and synthesized as a selective probe for the simultaneous detection of MNA and 4-NP. Utilizing 1H-NMR, 13C-NMR, and FT-IR analysis techniques, its structure was characterized. The binding property of BPOC to a variety of NACs, including 1,3-DNB, 2,3-DNT, 2,4-DNT, 2,6-DNT, 4-NP, 4-NT, and PA, revealed that the sensor binds to MNA and 4-NP with remarkable selectivity. Binding constant reveals lower detection limits of MNA is 0.2 µM and 0.3 µM for 4-NP. Using docking and density functional theory (DFT), computational insights were provided for investigating the stability and spectroscopic analysis of the inclusion complex. From molecular docking study, we observed the best docking score of BPOC with 4-NT and MNA complex. The calculations supplement the findings significantly and clarify the structural geometry and mode of interactions in supramolecular complexation. In an MTT experiment on human PBMC to check for cytotoxicity, this chemical was found to influence 1 × 10 5 cell viability dose-dependently., Competing Interests: Declarations. Consent for Participation: Not applicable. Consent for Publication: Not applicable. Conflict of Interest: There are no conflicts to declare., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Achalasia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absence of peristalsis, leading to significant swallowing difficulties and other symptoms. Traditional treatment options, including Heller myotomy (HM) and pneumatic dilation (PD), have been effective but are associated with risks such as perforation and gastroesophageal reflux disease (GERD). Peroral endoscopic myotomy (POEM) has emerged as a minimally invasive alternative, potentially offering several advantages over conventional methods. This systematic review aims to compare the efficacy, safety, and long-term outcomes of POEM versus HM in the treatment of achalasia. We systematically reviewed studies that compared POEM with HM in achalasia patients, focusing on key outcomes such as myotomy length, operative time, treatment success rates, and complication rates. The review included 15 studies comprising four randomized controlled trials, 10 cohort studies, and one case-control study. The results consistently showed that POEM achieved longer myotomy lengths and shorter operative times compared to HM. POEM also demonstrated higher or comparable treatment success rates, with a uniform definition of success based on achieving an Eckardt score of ≤3. However, the complication rates, particularly the incidence of GERD, varied between the two procedures, highlighting the need for careful patient selection and long-term follow-up. POEM offers a promising alternative to HM for the treatment of achalasia, with advantages in terms of reduced invasiveness, shorter operative times, and potentially higher treatment success rates. However, further high-quality research is necessary to fully establish its long-term efficacy and safety compared to conventional treatments., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kasapoglu et al.)

A genomic database of all Earth's eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP., (© 2024. The Author(s).)

Glycine max oil biofuel (GMOB) is a product of the transesterification of soybean oil. It contains a substantial amount of thermal energy. In this study, the result of varying fuel injection timings on the performance, ignition, and exhaust parameters of a research engine with single-cylinder, four-stroke with direct injection (DI) diesel was experimentally investigated and optimised using artificial neural networks (ANN). The results demonstrated that a 20% fuel blend with 24.5° before top dead centre (b TDC) decreased brake thermal efficiency (BTE), NO x emissions, and exhaust cylinder temperature but improved fuel consumption, carbon dioxide emissions (CDE), and smoke emissions. With 26.5° b TDC, the BTE was found to be approximately 5.0% higher while the fuel consumption was approximately 2.0% lower than with the original injection timing of 24.5° b TDC. At 26.5° b TDC, the NO x emission was approximately 8.6% higher, and the smoke emission was approximately 4.07% lower than at the original injection timing (24.5° b TDC)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: MecROX is a mechanistic sub-study of the UK-ROX trial which was designed to evaluate the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care. This is based on the scientific rationale that excess oxygen is harmful. Epithelial cell damage with alveolar surfactant deficiency is characteristic of hyperoxic acute lung injury. Additionally, hyperoxaemia (excess blood oxygen levels) may exacerbate whole-body oxidative stress leading to cell death, autophagy, mitochondrial dysfunction, bioenergetic failure and multi-organ failure resulting in poor clinical outcomes. However, there is a lack of in-vivo human models evaluating the mechanisms that underpin oxygen-induced organ damage in mechanically ventilated patients., Aim: The aim of the MecROX mechanistic sub-study is to assess lung surfactant composition and global systemic redox status to provide a mechanistic and complementary scientific rationale to the UK-ROX trial findings. The objectives are to quantify in-vivo surfactant composition, synthesis, and metabolism with markers of oxidative stress and systemic redox disequilibrium (as evidenced by alterations in the 'reactive species interactome') to differentiate between groups of conservative and usual oxygen targets., Methods and Design: After randomisation into the UK-ROX trial, 100 adult participants (50 in the conservative and 50 in usual care group) will be recruited at two trial sites. Blood and endotracheal samples will be taken at 0, 48 and 72 hours following an infusion of 3 mg/kg methyl -D 9 -choline chloride. This is a non-radioactive, stable isotope of choline (vitamin), which has been extensively used to study surfactant phospholipid kinetics in humans. This study will mechanistically evaluate the in-vivo surfactant synthesis and breakdown (by hydrolysis and oxidation), oxidative stress and redox disequilibrium from sequential plasma and bronchial samples using an array of analytical platforms. We will compare conservative and usual oxygenation groups according to the amount of oxygen administered. Trial registration: ISRCTNISRCTN61929838, 27/03/2023 https://doi.org/10.1186/ISRCTN61929838., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Dushianthan A et al.)

Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-β 42 oligomer-induced bioenergetic changes, suggesting that amyloid-β 42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APP Swe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1 + cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Tadalafil (TDL) has poor bioavailability due to the less aqueous solubility and bitter taste. Oral solid dosage forms, especially tablets, have a broad market worldwide. Constraints of tablets are a long process, pollution, high processing cost, and requiring more excipient. The research was performed to optimize an eco-friendly immediate-acting pastille of TDL to put forward an alternate formulation to a tablet using advanced data mining tools. Another objective is to assess the taste masking of TDL using the Brief Access Taste Aversion ( BATA) model. The amount of PEG-4000, Polyox N-10, and Kyron T-314 were chosen as critical material attributes from failure mode effect analysis. Box-Behnken design (BBD) was utilized to optimize the pastilles and ascertained the significant impact of chosen variables on disintegration time and % CDR at 10 min. The control strategy and optimal region were located using an overlay plot. The pastilles were able to release the drug within 15 min due to faster disintegration. The formulated pastilles were of uniform size, shape, and mechanical strength. The bitter taste of TDL was masked and confirmed by the BATA model. The newer formulation may be helpful in the industry due to its eco-friendly, single-step, and economical process. It unlocks a new direction in the field of oral solid dosage form as an alternative to tablets., Competing Interests: The authors do not have any declarations of interest., (© 2024 The Authors.)

The nanoparticle (NP) redox state is an important parameter in the performance of cobalt-based Fischer-Tropsch synthesis (FTS) catalysts. Here, the compositional evolution of individual CoNPs (6-24 nm) in terms of the oxide vs metallic state was investigated in situ during CO/syngas treatment using spatially resolved X-ray absorption spectroscopy (XAS)/X-ray photoemission electron microscopy (X-PEEM). It was observed that in the presence of CO, smaller CoNPs (i.e., ≤12 nm in size) remained in the metallic state, whereas NPs ≥ 15 nm became partially oxidized, suggesting that the latter were more readily able to dissociate CO. In contrast, in the presence of syngas, the oxide content of NPs ≥ 15 nm reduced, while it increased in quantity in the smaller NPs; this reoxidation that occurs primarily at the surface proved to be temporary, reforming the reduced state during subsequent UHV annealing. O K-edge measurements revealed that a key parameter mitigating the redox behavior of the CoNPs were proximate oxygen vacancies (O vac ). These results demonstrate the differences in the reducibility and the reactivity of Co NP size on a Co/TiO 2 catalyst and the effect O vac have on these properties, therefore yielding a better understanding of the physicochemical properties of this popular choice of FTS catalysts., Competing Interests: The authors declare the following competing financial interest(s): Andrew M. Beale is a co-owner of Finden Ltd., a contract research organization that performs characterization studies on functional materials., (© 2023 The Authors. Published by American Chemical Society.)

This research presents the application of Dinaphthoylated Oxacalix[4]arene (DNOC) as a novel fluorescent receptor for the purpose of selectively detecting nitroaromatic compounds (NACs). The characterization of DNOC was conducted through the utilization of spectroscopic methods, including 1 H-NMR, 13 C-NMR, and ESI-MS. The receptor demonstrated significant selectivity in acetonitrile towards several nitroaromatic analytes, such as MNA, 2,4-DNT, 2,3-DNT, 1,3-DNB, 2,6-DNT, and 4-NT. This selectivity was validated by the measurement of emission spectra. The present study focuses on the examination of binding constants, employing Stern-Volmer analysis, as well as the determination of the lowest detection limit (3σ/Slope) and fluorescence quenching. These investigations aim to provide insights into the inclusion behavior of DNOC with each of the six analytes under fluorescence spectra investigation. Furthermore, the selectivity trend of the ligand DNOC for NAC detection is elucidated using Density Functional Theory (DFT) calculations conducted using the Gaussian 09 software. The examination of energy gaps existing between molecular orbitals, namely the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), provides a valuable understanding of electron-transfer processes and electronic interactions. Smaller energy gaps are indicative of heightened selectivity resulting from favorable electron-transfer processes, whereas bigger gaps suggest less selectivity attributable to weaker electronic contacts. This work integrates experimental and computational methodologies to provide a full understanding of the selective binding behavior of DNOC. As a result, DNOC emerges as a viable chemical sensor for detecting nitroaromatic explosives., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genome sequencing enables answering fundamental questions about the genetic basis of adaptation, population structure and epigenetic mechanisms. Yet, we usually need a suitable reference genome for mapping population-level resequencing data. In some model systems, multiple reference genomes are available, giving the challenging task of determining which reference genome best suits the data. Here, we compared the use of two different reference genomes for the three-spined stickleback (Gasterosteus aculeatus), one novel genome derived from a European gynogenetic individual and the published reference genome of a North American individual. Specifically, we investigated the impact of using a local reference versus one generated from a distinct lineage on several common population genomics analyses. Through mapping genome resequencing data of 60 sticklebacks from across Europe and North America, we demonstrate that genetic distance among samples and the reference genomes impacts downstream analyses. Using a local reference genome increased mapping efficiency and genotyping accuracy, effectively retaining more and better data. Despite comparable distributions of the metrics generated across the genome using SNP data (i.e. π, Tajima's D and F ST ), window-based statistics using different references resulted in different outlier genes and enriched gene functions. A marker-based analysis of DNA methylation distributions had a comparably high overlap in outlier genes and functions, yet with distinct differences depending on the reference genome. Overall, our results highlight how using a local reference genome decreases reference bias to increase confidence in downstream analyses of the data. Such results have significant implications in all reference-genome-based population genomic analyses., (© 2023 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Introduction: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities., Methods: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting., Results: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03)., Conclusion: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Titanium-based metals are used most often in biomedical implant studies because they have good qualities like being biocompatible, not being poisonous, Osseo-integration, high specific properties, wear resistance, etc. The main goal of this work is to improve the wear resistance of Ti-6Al-7Nb biomedical metal by using a mix of Taguchi, ANOVA, and Grey Relational Analysis. The effect of changeable control process factors like applied load, spinning speed, and time on wear reaction measures like wear rate (WR), coefficient of friction (COF), and frictional force. The optimal combinations of wear rate, COF, and frictional force minimise wear characteristics. The L9 Taguchi orthogonal array was used to plan the experiments, which were done on a pin-on-disc set-up according to ASTM G99. To find the best set of control factors, Taguchi, ANOVA, and Grey relationship analysis were used. The results show that a load of 30 N, a speed of 700 rpm, and a time of 10 min are the best control settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

In clinical research and care, information notices are too often reduced to complicated and hard-to-understand mandatory documents. However, every person has the right to transparent and truthful information. These considerations prompted the creation of a multidisciplinary working group in the fall of 2020, headed by the College des relecteurs de l'Inserm. This group associates the different actors involved in the development, evaluation and use of information notices: Health and research professionals, representatives of patient associations or research foundations, ethicists, jurists, scientific educators and communicators. This group has created a set of texts, pictograms and illustrations, adapted to the people concerned and accepted by all actors. These contents will be easily used by professionals through the app Notice infobox© . A pilot phase was conducted to generate the notices of the France Genomic Medicine Plan 2025, used for genetic examinations. This app Notice infobox© is a response to society's request to be an actor in its own healthcare and to adopt more ethical and responsible research., (© 2023 médecine/sciences – Inserm.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

A pyrene functionalized oxacalix[4]arene architecture (DPOC) was utilized as a fluorescence probe for selective recognition of cyanide ions. The receptor DPOC shows excellent selectivity towards cyanide ion with a red shift of 108 nm in absorption band along with a significant change in colour from light yellow to pink. The fluorescence titration experiments further confirm the lower limit of detection as 1.7µM with no significant influences of competing anions. 1  H-NMR titration experiments support the deprotonation phenomena, as the -NH proton disappears upon successive addition of cyanide ions. The DFT calculation also indicates a certain increment of -NH bond length upon interaction with cyanide ions. The spectral properties as well as colour of DPOC-CN - system may be reversed upon the addition of Ag + / Cu 2+ ions up to 5 consecutive cycles. Moreover, DPOC coated "test strips" were prepared for visual detection of cyanide ions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Herein, a novel N-(4-(tert-butyl)-phenyl)-2-chloroacetamide functionalized thiacalix[4]arene architecture, viz TCAN2PA has been synthesized and the sensing behaviour towards metal ions were explored. The probe, TCAN2PA displayed "turn-on" fluorescence response towards Hg(II) ions in acetonitrile over a series of competing common metal ions. A bathochromic shift in absorption band along with a significant "Turn-On" fluorescence behaviour of TCAN2PA was observed upon interaction with Hg(II) ions. The lower rim modification of thiacalixarene with N-(4-(tert-butyl)-phenyl)-2-chloroacetamide actively contributes toward the fluorescence property due to the presence of strong electron-donating aryl amido substituent. Fluorescence titration experiments were conducted to find out the limit of detection and to understand binding stoichiometry as well. The electron transfer interactions between the electron rich TCAN2PA host with Hg(II) ions have been postulated which is also supported by computational modelling insights., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this era, explosives are easily available compared to the early days. Thus, more effective detection of explosives has become the main concern of homeland security. In the past decades, a large number of sensing materials have been developed for the detection of explosives in solid, vapor, and solution states through fluorescence methods. In recent years, great efforts have been devoted to developing new fluorescent materials with various sensing mechanisms for detecting explosives in order to achieve super-sensitivity, ultra-selectivity, as well as fast response time. Modified calixarenes have high potentials to detect nitroaromatic compounds (NACs) due to their favorable structural properties. It summarizes the detection of NACs by the modified calixarene system formed by the complex. Various methodologies responsible for complex formation and binding mechanisms (PET, FRET, EE, etc.) are the centerpiece of this review. Finally, conclusions and future outlook are presented and discussed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To conduct an independent study investigating how adults perceive the usability and functionality of the 'National Health Service (NHS) COVID-19' application (app). This study aims to highlight strengths and provide recommendations to improve adoption of future contact tracing developments., Design: A 60-item, anonymous online questionnaire, disseminated through social media outlets and email lists by a team from Imperial College London., Setting: England., Participants: Convenience sample of 1036 responses, from participants aged 18 years and above, between December 2020 and January 2021., Primary Outcome Measures: Evaluate the compliance and public attitude towards the 'NHS COVID-19' app regarding its functionality and features. This included whether participants' expectations were met, and their thoughts on the app privacy and security. Furthermore, to distinguish how usability, perception, and adoption differed with varying demographics and user values., Results: Fair compliance with the app features was identified, meeting expectations of the 62.1% of participants who stated they downloaded it after weighted analysis. However, participants finding the interface challenging were less likely to read information in the app and had a lesser understanding of its functionality. Furthermore, little understanding regarding the app's functionality and privacy concerns was a possible reason why users did not download it. A readability analysis of the text revealed information within the app was conveyed at a level that may be too complex for up to 43% of the UK population. The study highlighted issues related to the potential of false positives caused by the design choices in the 'Check-In' feature., Conclusion: This study showed that while the 'NHS COVID-19' app was viewed positively, there remained issues regarding participants' perceived knowledge of app functionality, potentially affecting compliance. Therefore, we recommended improvements regarding the delivery and presentation of the app's information, and highlighted the potential need for the ability to check out of venues to reduce the number of false positive contacts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management., Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021., Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05)., Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Platinum group metals such as palladium and rhodium based catalysts are currently being implemented in gasoline particulate filter (GPF) autoexhaust after treatment systems. However, little is known about how the trapped particulate matter, such as the incombustible ash, interacts with the catalyst and so may affect its performance. This operando study follows the evolution of the Pd found in two different model GPF systems: one containing ash components extracted from a GPF and another from a catalyst washcoat prior to adhesion onto the GPF. We show that the catalytic activity of the two systems vary when compared with a 0 g ash containing GPF. Compared to the 0 g ash sample the 20 g ash containing sample had a higher CO light off temperature, in addition, an oscillation profile for CO, CO 2 and O 2 was observed, which is speculated to be a combination of CO oxidation, C deposition via a Boudouard reaction and further partial oxidation of the deposited species to CO. During the ageing procedure the washcoat sample reduces NO at a lower temperature than the 0 g ash sample. However, post ageing the 0 g ash sample recovers and both samples reduce NO at 310 °C. In comparison, the 20 g ash GPF sample maintains a higher NO reduction temperature of 410 °C post ageing, implying that the combination of high temperature ageing and presence of ash has an irreversible negative effect on catalyst performance., (Creative Commons Attribution license.)

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Parasite Plasmodium falciparum is continuously giving a challenge to human beings by changing itself against most of the antimalarial drugs and its consequences can be seen in the form of a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis by blocking the gene expression. S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase that catalyzes methylation of the capped structure at the 5'-terminus of mRNA, and other methylation reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed which are based on the inhibition of SAH hydrolase. This review summarises the development of SAH inhibitors developed over the last 20 years and their potentiality for the treatment of malaria., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Mass spectrometry imaging (MSI) visualizes molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labeling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic pulmonary surfactants were imaged from distributions of intact and metabolic products of an added tracer, universally 13 C-labeled dipalmitoyl PC (U 13 C-DPPC). The parenchymal distributions of newly synthesized PC species were also imaged from incorporations of methyl-D 9 -choline. This dual labeling strategy demonstrated both lack of inhibition of endogenous PC synthesis by exogenous surfactant and location of acyl chain remodeling processes acting on the U 13 C-DPPC-labeled surfactant, leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events will greatly enhance our understanding of lipid metabolism in diverse tissues and has potential application to both clinical and experimental studies., Competing Interests: Conflict of interest J. W. and H. W. C. received funding from the Chiesi Farmaceutica for the original study from which lung tissue samples were provided for MSI. There are no other competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Endoparasitoid wasps are important natural enemies of many insect species and are major selective forces on the host immune system. Despite increased interest in insect antiparasitoid immunity, there is sparse information on the evolutionary dynamics of biological pathways and gene regulation involved in host immune defense outside Drosophila species. We de novo assembled transcriptomes from two beetle species and used time-course differential expression analysis to investigate gene expression differences in closely related species Galerucella pusilla and G. calmariensis that are, respectively, resistant and susceptible against parasitoid infection by Asecodes parviclava parasitoids. Approximately 271 million and 224 million paired-ended reads were assembled and filtered to form 52,563 and 59,781 transcripts for G. pusilla and G. calmariensis, respectively. In the whole-transcriptome level, an enrichment of functional categories related to energy production, biosynthetic process, and metabolic process was exhibited in both species. The main difference between species appears to be immune response and wound healing process mounted by G. pusilla larvae. Using reciprocal BLAST against the Drosophila melanogaster proteome, 120 and 121 immune-related genes were identified in G. pusilla and G. calmariensis, respectively. More immune genes were differentially expressed in G. pusilla than in G. calmariensis, in particular genes involved in signaling, hematopoiesis, and melanization. In contrast, only one gene was differentially expressed in G. calmariensis. Our study characterizes important genes and pathways involved in different immune functions after parasitoid infection and supports the role of signaling and hematopoiesis genes as key players in host immunity in Galerucella against parasitoid wasps., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Aim: To describe the experience of a single fetal medicine unit in evaluating pregnant women with potential exposure to Zika virus (ZIKV) following travel., Method: Between February 2016 and June 2017, a multidisciplinary team evaluated pregnant women by developing a local pathway based on Public Health England guidance. All pregnant women were offered serial fetal ultrasound scans (USS). If they presented with a history of clinical symptoms consistent with ZIKV infection during or within two weeks of travel or fetal USS was suggestive of microcephaly, reverse transcriptase polymerase chain reaction (RT PCR) and/or serology was used., Results: 69 women were referred. Eight patients reported symptoms consistent with ZIKV infection (11.6%) and six (8.7%) patients reported mosquito bites. Maternal exposure was mainly during the preconception period and the first trimester in 35 (50.8%) and 19 (27.5%) women, respectively. Prenatally, there was no evidence of microcephaly in any of the 69 referrals. Sixty-two live births and seven miscarriages were reported. One patient had serology confirming ZIKV infection during pregnancy. At birth, 57 babies had normal head circumference (HC) measurements, including the baby born to the Zika positive mother. Two babies had small HC measurements but were not infected and were small for gestational age., Conclusions: One case of maternal ZIKV infection was detected but without any fetal congenital abnormalities postnatally. The number of potentially infected patients referred to our unit is a demonstration of the concern regarding perinatal ZIKV infection in the pregnant population.

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.

Competing Interests: Competing interests: None declared.

As a part of the ELIXIR-EXCELERATE efforts in capacity building, we present here 10 steps to facilitate researchers getting started in genome assembly and genome annotation. The guidelines given are broadly applicable, intended to be stable over time, and cover all aspects from start to finish of a general assembly and annotation project. Intrinsic properties of genomes are discussed, as is the importance of using high quality DNA. Different sequencing technologies and generally applicable workflows for genome assembly are also detailed. We cover structural and functional annotation and encourage readers to also annotate transposable elements, something that is often omitted from annotation workflows. The importance of data management is stressed, and we give advice on where to submit data and how to make your results Findable, Accessible, Interoperable, and Reusable (FAIR)., Competing Interests: No competing interests were disclosed.

Unruptured aneurysm usually presents with headache and neuro-ophthalmic features; when it ruptures, it presents with subarachnoid haemorrhage. Basilar artery aneurysm represents only 3-5% of cerebral aneurysms. Non-haemorrhagic symptoms and the signs of unruptured aneurysms are manifested as mass effect, thromboembolic phenomenon or epileptical attacks. Clinical presentation of unruptured aneurysm depends on structures which are involved. In our case, the patient had insidious onset headache and spastic quadriparesis with sixth cranial nerve palsy, which implicate involvement of corticospinal pathways at the level of pons., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: A national consensus panel was convened to develop recommendations on future directions for home-based dementia care (HBDC)., Methods: The panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus-based recommendations., Results: The panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed., Discussion: HBDC represents a promising paradigm shift to improve care for those living with dementia and their family caregivers: these recommendations provide a framework to chart a course forward for HBDC., (Copyright © 2017 the Alzheimer's Association. All rights reserved.)

Commonly reported complications of hepatic cysts are spontaneous hemorrhage, rupture into the peritoneal cavity, infection and compression of the biliary tree however cardiac complications are not commonly reported. We are presenting a case of a large liver cyst presenting with right atrial and ventricular inflow tract impingement resulting in cardiac symptoms. A 68 year-old Hispanic female presented with one month of fatigue and shortness of breath after household work and walking less than one block, right upper quadrant pain and weight loss. She had history of multiple hepatic cysts for more than 12 years, well-controlled diabetes and hypertension. Examination of the heart revealed tachycardia with regular heart sounds. There were no murmurs. She had tenderness in her right upper quadrant on palpation and an enlarged smooth liver. Rest of physical examination was unremarkable. CT scan of the abdomen showed multiple non-enhancing liver cysts in both lobes, with the largest measuring 12 x 15 x 17 cm which was significantly increased from her baseline of 7 x 8 x 10 cm in 2003. Echocardiogram showed normal left ventricular ejection fraction, grade 1 diastolic dysfunction and a hepatic cyst impinging RA and RV inflow tract. She had successful laparoscopic enucleation of liver cyst and subsequent relief from tachycardia, fatigue and shortness of breath. In conclusion, this case illustrates that hepatic cysts may become symptomatic after remaining quiescent for an extended period. They may present with unusual symptoms and clinicians should be mindful of rare complications, such as in this case.

A new fluorescence receptor calix[4]pyrrole-N-(quinoline-8-yl) acetamide (CAMQ) containing a pyrrolic ring connected via the meso-position was synthesized, purified and characterized by elemental analysis, NMR and mass spectroscopy. This compound was examined for its fluorescence properties towards different metal ions e.g. Ag(I), Hg(II), Co(II), Ca(II), Ni(II), Zn(II), Cr(II), Ba(II), Fe(II), Cu(II), Pb(II)and Mg(II) ions by spectrophotometry and spectrofluorometry. It was concluded that the compound (CAMQ) possessed significantly enhanced selectivity for Pb(II) and Cu(II) ions in dimethyl sulfoxide (DMSO) even at very low concentrations (1 μM). It exhibit 'turn-on' fluorescence when exposed to Pb(II) and Cu(II) and did so in preference to other metal ions. The binding constants, stoichiometry and quantum yields have been determined. The quenching mechanism was assessed using the Stern-Volmer equation and was also discussed., (Copyright © 2017 John Wiley & Sons, Ltd.)

We report a case of 29-year-old woman referred to us for management of refractory epilepsy. Under observation, she was detected to have recurrent hypoglycaemia during the episodes of seizures. On investigation, she was found to have hyperinsulinemic hypoglycaemia. Her triple-phase CT scan of abdomen showed neuroendocrine tumour of pancreatic head, with bilateral renal calculi. Screening of other endocrine glands revealed pituitary microadenoma and parathyroid adenoma on imaging, which was also supported by biochemical and hormonal profile. On the basis of tumours involving parathyroid, pancreatic islets and pituitary gland, she was diagnosed as a case of multiple endocrine neoplasia type 1. Pancreatic tumour removal was done and bromocriptine was started. She was followed up for 6 months postoperatively and never had seizures even without antiepileptic drugs. This case report highlights an exceptional treatable cause of uncontrolled seizures., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Central pontine myelinolysis (CPM) is a demyelinating disorder of central nervous system which involves central portion of the pons and sometimes extrapontine areas also. It is commonly reported in settings of hyponatraemia or its rapid correction, but in the last few years it has also been reported in patients with diabetes in the absence of electrolyte disturbances or correction of serum osmolality. Here we report a case of a 20-year-old female patient, with a known history of type 1 diabetes mellitus, who presented with acute onset spastic quadriparesis with dysarthria and mild ataxia which evolved over 2 weeks. Her MRI brain showed well-defined, bilateral symmetric hyperintense lesion involving central pons showing area of diffusion restriction which was consistent with CPM. Patient was treated conservatively and improved over a period of few weeks. To diagnose more number of cases, we should not overlook CPM in patients with diabetes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Identifying preventive targets for Alzheimer's disease is a central challenge of modern medicine. Non-steroidal anti-inflammatory drugs, which inhibit the cyclooxygenase enzymes COX-1 and COX-2, reduce the risk of developing Alzheimer's disease in normal ageing populations. This preventive effect coincides with an extended preclinical phase that spans years to decades before onset of cognitive decline. In the brain, COX-2 is induced in neurons in response to excitatory synaptic activity and in glial cells in response to inflammation. To identify mechanisms underlying prevention of cognitive decline by anti-inflammatory drugs, we first identified an early object memory deficit in APPSwe-PS1ΔE9 mice that preceded previously identified spatial memory deficits in this model. We modelled prevention of this memory deficit with ibuprofen, and found that ibuprofen prevented memory impairment without producing any measurable changes in amyloid-β accumulation or glial inflammation. Instead, ibuprofen modulated hippocampal gene expression in pathways involved in neuronal plasticity and increased levels of norepinephrine and dopamine. The gene most highly downregulated by ibuprofen was neuronal tryptophan 2,3-dioxygenase (Tdo2), which encodes an enzyme that metabolizes tryptophan to kynurenine. TDO2 expression was increased by neuronal COX-2 activity, and overexpression of hippocampal TDO2 produced behavioural deficits. Moreover, pharmacological TDO2 inhibition prevented behavioural deficits in APPSwe-PS1ΔE9 mice. Taken together, these data demonstrate broad effects of cyclooxygenase inhibition on multiple neuronal pathways that counteract the neurotoxic effects of early accumulating amyloid-β oligomers., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A series of novel substituted oxacalix[4]arene has been synthesized and explored for their biological profile by evaluating anticancer, antifungal and antibacterial properties. The derivatives have been characterized by various spectroscopic techniques such as IR, (1)H NMR, (13)C NMR and Mass spectrometry. Many compounds showed strong inhibition (MIC) in the range of ∼0-50 μM with interesting cytotoxic activities against Hela cells in particular. The compounds were theoretically evaluated by docking studies as potential histone deacetylase inhibitors (HDACi). The study indicates that compounds bound adequately with HDAC, and hence complemented the experimental findings., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The observation of habitat-specific phenotypes suggests the action of natural selection. The three-spined stickleback (Gasterosteus aculeatus) has repeatedly colonized and adapted to diverse freshwater habitats across the northern hemisphere since the last glaciation, while giving rise to recurring phenotypes associated with specific habitats. Parapatric lake and river populations of sticklebacks harbour distinct parasite communities, a factor proposed to contribute to adaptive differentiation between these ecotypes. However, little is known about the transcriptional response to the distinct parasite pressure of those fish in a natural setting. Here, we sampled wild-caught sticklebacks across four geographical locations from lake and river habitats differing in their parasite load. We compared gene expression profiles between lake and river populations using 77 whole-transcriptome libraries from two immune-relevant tissues, the head kidney and the spleen. Differential expression analyses revealed 139 genes with habitat-specific expression patterns across the sampled population pairs. Among the 139 differentially expressed genes, eight are annotated with an immune function and 42 have been identified as differentially expressed in previous experimental studies in which fish have been immune challenged. Together, these findings reinforce the hypothesis that parasites contribute to adaptation of sticklebacks in lake and river habitats., (© 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.)

Background: Endoparasites with complex life cycles are faced with several biological challenges, as they need to occupy various ecological niches throughout their development. Host phenotypes that increase the parasite's transmission rate to the next host have been extensively described, but few mechanistic explanations have been proposed to describe their proximate causes. In this study we explore the possibility that host phenotypic changes are triggered by the production of mimicry proteins from the parasite by using an ecological model system consisting of the infection of the threespine stickleback (Gasterosteus aculeatus) by the cestode Schistocephalus solidus., Method: Using RNA-seq data, we assembled 9,093 protein-coding genes from which ORFs were predicted to generate a reference proteome. Based on a previously published method, we built two complementary analysis pipelines to i) establish a general classification of protein similarity among various species (pipeline A) and ii) identify candidate mimicry proteins showing specific host-parasite similarities (pipeline B), a key feature underlying the possibility of molecular mimicry., Results: Ninety-four tapeworm proteins showed high local sequence homology with stickleback proteins. Four of these candidates correspond to secreted or membrane proteins that could be produced by the parasite and eventually be released in or be in contact with the host to modulate physiological pathways involved in various phenotypes (e.g. behaviors). One of these candidates belongs to the Wnt family, a large group of signaling molecules involved in cell-to-cell interactions and various developmental pathways. The three other candidates are involved in ion transport and post-translational protein modifications. We further confirmed that these four candidates are expressed in three different developmental stages of the cestode by RT-PCR, including the stages found in the host., Conclusion: In this study, we identified mimicry candidate peptides from a behavior-altering cestode showing specific sequence similarity with host proteins. Despite their potential role in modulating host pathways that could lead to parasite-induced phenotypic changes and despite our confirmation that they are expressed in the developmental stage corresponding to the altered host behavior, further investigations will be needed to confirm their mechanistic role in the molecular cross-talk taking place between S. solidus and the threespine stickleback.

The human malaria parasite Plasmodium falciparum possesses sophisticated systems of protein secretion to modulate host cell invasion and remodeling. In the present study, we provide insights into the function of the AP-1 complex in P. falciparum. We utilized GFP fusion constructs for live cell imaging, as well as fixed parasites in immunofluorescence analysis, to study adaptor protein mu1 (Pfμ1) mediated protein trafficking in P. falciparum. In trophozoites Pfμ1 showed similar dynamic localization to that of several Golgi/ER markers, indicating Golgi/ER localization. Treatment of transgenic parasites with Brefeldin A altered the localization of Golgi-associated Pfμ1, supporting the localization studies. Co-localization studies showed considerable overlap of Pfμ1 with the resident rhoptry proteins, rhoptry associated protein 1 (RAP1) and Cytoadherence linked asexual gene 3.1 (Clag3.1) in schizont stage. Immunoprecipitation experiments with Pfμ1 and PfRAP1 revealed an interaction, which may be mediated through an intermediate transmembrane cargo receptor. A specific role for Pfμ1 in trafficking was suggested by treatment with AlF4, which resulted in a shift to a predominantly ER-associated compartment and consequent decrease in co-localization with the Golgi marker GRASP. Together, these results suggest a role for the AP-1 complex in rhoptry protein trafficking in P. falciparum., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The patterns of genomic divergence during ecological speciation are shaped by a combination of evolutionary forces. Processes such as genetic drift, local reduction of gene flow around genes causing reproductive isolation, hitchhiking around selected variants, variation in recombination and mutation rates are all factors that can contribute to the heterogeneity of genomic divergence. On the basis of 60 fully sequenced three-spined stickleback genomes, we explore these different mechanisms explaining the heterogeneity of genomic divergence across five parapatric lake and river population pairs varying in their degree of genetic differentiation. We find that divergent regions of the genome are mostly specific for each population pair, while their size and abundance are not correlated with the extent of genome-wide population differentiation. In each pair-wise comparison, an analysis of allele frequency spectra reveals that 25-55% of the divergent regions are consistent with a local restriction of gene flow. Another large proportion of divergent regions (38-75%) appears to be mainly shaped by hitchhiking effects around positively selected variants. We provide empirical evidence that alternative mechanisms determining the evolution of genomic patterns of divergence are not mutually exclusive, but rather act in concert to shape the genome during population differentiation, a first necessary step towards ecological speciation.