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Reservoir simulation is crucial for understanding the flow response in underground reservoirs, and it significantly helps reduce uncertainties in geological characterization and optimize methodologies for field development strategies. However, providing efficient and accurate solutions for the strong heterogeneity remains challenging, as most of the discretization methods cannot handle this complexity. In this work, we perform a comprehensive assessment of various numerical linearization techniques employed in reservoir simulation, particularly focusing on the performance of the nonlinear solver for problem dealing with fluid flow in porous media. The primary linearization methods examined are finite difference central (FDC), finite forward difference (FDF), and operator-based linearization (OBL). These methods are rigorously analyzed and compared in terms of their accuracy, computational efficiency, and adaptability to changing reservoir conditions. The results demonstrate that each method has distinct strengths and limitations. The FDC method is more accurate particularly in complex simulations where strong heterogeneity are introduced but is generally slower in convergence. The OBL on the other hand, is more efficient and converges quickly, which makes it suitable for scenarios with limited computational resources and simple physics, while the FDF method provides a balanced combination of precision and computational speed, contingent upon careful step size management of the derivative estimations. This paper aims to guide the selection of appropriate linearization techniques for enhancing nonlinear solvers' accuracy and efficiency in reservoir simulation ., (© 2024. The Author(s).)

Objectives: Authentic work-based learning is crucial to facilitate the development and preparedness for training healthcare professionals. Such experiences are challenging to design and secure within the clinical environment. One School of Pharmacy established a student-led clinic to provide undergraduate pharmacy students the opportunity to practise physical assessment and communication skills with members of the public. The aim of this study was to explore students' thoughts and perspectives on this experience., Methods: Undergraduate students were invited to participate in a semi-structured interview after their clinic experience. Transcriptions of the interviews were analysed by reflexive thematic analysis., Results: Twelve students agreed to an interview that took place between October and December 2022. Three themes were identified from the qualitative data which related to external factors that influenced student experience of the clinic, for example, organizational issues and impact of the physical environment; interactions within the clinic environment; and internalized learning for example, professional growth and development, and the appreciating the learning opportunity., Conclusions: In the current climate, where securing valuable work-based learning opportunity is challenging, student-led clinics offer an environment that is well-received by students and appears to facilitate student professional development. Student clinics are receiving more attention and investment across undergraduate healthcare programmes around the world given advantages such as these. However, they need to be well integrated and structured into the existing training and education and students need appropriate induction to prepare them for the experience and manage expectations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Arsenic, ubiquitous in various industrial processes and consumer products, presents both essential functions and considerable toxicity risks, driving extensive research into safer applications. Our investigation, drawing from 7182 arsenic-containing molecules in the Cambridge Structural Database (CSD), outlines their diverse bonding patterns. Notably, 51% of these molecules exhibit cyclic connections, while 49% display acyclic ones. Arsenic forms eight distinct bonding types with other elements, with significant interactions observed, particularly with phenyl rings, O 3 and F 6 moieties. Top interactions involve carbon, nitrogen, oxygen, fluorine, sulfur, and arsenic itself. We meticulously evaluated average bond lengths under three conditions: without an R-factor cut-off, with R-factor ≤0.075, and with R-factor ≤0.05, supporting the credibility of our results. Comparative analysis with existing literature data enriches our understanding of arsenic's bonding behaviour. Our findings illuminate the structural attributes, molecular coordination, geometry, and bond lengths of arsenic with 68 diverse atoms, enriching our comprehension of arsenic chemistry. These revelations not only offer a pathway for crafting innovative and safer arsenic-based compounds but also foster the evolution of arsenic detoxification mechanisms, tackling pivotal health and environmental challenges linked to arsenic exposure across different contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hemolysis is a crucial factor in various biomedical and pharmaceutical contexts, driving our interest in developing advanced computational techniques for precise prediction. Our proposed approach takes advantage of the unique capabilities of convolutional neural networks (CNNs) and transformers to detect complex patterns inherent in the data. The integration of CNN and transformers' attention mechanisms allows for the extraction of relevant information, leading to accurate predictions of hemolytic potential. The proposed method was trained on three distinct data sets of peptide sequences known as recurrent neural network-hemolytic (RNN-Hem), Hlppredfuse, and Combined. Our computational results demonstrated the superior efficacy of our models compared to existing methods. The proposed approach demonstrated impressive Matthews correlation coefficients of 0.5962, 0.9111, and 0.7788 respectively, indicating its effectiveness in predicting hemolytic activity. With its potential to guide experimental efforts in peptide design and drug development, this method holds great promise for practical applications. Integrating CNNs and transformers proves to be a powerful tool in the fields of bioinformatics and therapeutic research, highlighting their potential to drive advancement in this area., (© 2024. The Author(s).)

This study explicates an Islamic approach to palliative care based on the results of a needs analysis regarding the development of an Islamic psychospiritual manual of palliative care alongside related elements. This article represents the first phase of a three-phase study using the design and development research (DDR) approach developed by Richey and Klein to study for design and development of manual either needed or otherwise. This project is a quantitative study that uses purposive sampling through a questionnaire instrument to investigate 210 participants from the general population in Malaysia that have experience in taking care of terminally ill patients. The findings of the study indicated that the majority of participants agreed with the development of an Islamic psychospiritual manual with mean values (x̅) of 4.57 and 4.66. Concurrently, the findings showed that the hierarchy of emphasis in terms of the elements to be included in the manual starts with emotional support, which exhibited the highest mean rate (x̅), followed by faith in God, spiritual and religious support, self and physical management, trauma management and social support. The correlations indicated that all the elements to be included in the manual were significant., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Revolutionizing construction, the concrete blend seamlessly integrates human hair (HH) fibers and millet husk ash (MHA) as a sustainable alternative. By repurposing human hair for enhanced tensile strength and utilizing millet husk ash to replace sand, these materials not only reduce waste but also create a durable, eco-friendly solution. This groundbreaking methodology not only adheres to established structural criteria but also advances the concepts of the circular economy, representing a significant advancement towards environmentally sustainable and resilient building practices. The main purpose of the research is to investigate the fresh and mechanical characteristics of concrete blended with 10-40% MHA as a sand substitute and 0.5-2% HH fibers by applying response surface methodology modeling and optimization. A comprehensive study involved preparing 225 concrete specimens using a mix ratio of 1:1.5:3 with a water-to-cement ratio of 0.52, followed by a 28 day curing period. It was found that a blend of 30% MHA and 1% HH fibers gave the best compressive and splitting tensile strengths at 28 days, which were 33.88 MPa and 3.47 MPa, respectively. Additionally, the incorporation of increased proportions of MHA and HH fibers led to reductions in both the dry density and workability of the concrete. In addition, utilizing analysis of variance (ANOVA), response prediction models were created and verified with a significance level of 95%. The models' R 2 values ranged from 72 to 99%. The study validated multi-objective optimization, showing 1% HH fiber and 30% MHA in concrete enhances strength, reduces waste, and promotes environmental sustainability, making it recommended for construction., (© 2024. The Author(s).)

Zoonotic monkeypox disease, caused by the double-stranded DNA monkeypox virus, has become a global concern. Due to the absence of a specific small molecule drug for the disease, this report aims to identify potential inhibitor drugs for monkeypox. This study explores a drug repurposing strategy using virtual screening to evaluate 1615 FDA approved drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R. Normal mode analysis and molecular dynamics simulation assessed the flexibility and stability of the target protein in complex with the top screened drugs. The analysis identified Nilotinib (ZINC000006716957), Conivaptan (ZINC000012503187), and Ponatinib (ZINC000036701290) as the most potential RNA polymerase inhibitors with binding energies of - 7.5 kcal/mol. These drugs mainly established hydrogen bonds and hydrophobic interactions with the protein active sites, including LEU95, LEU90, PRO96, MET110, and VAL113, and residues nearby. Normal mode analysis and molecular dynamics simulation confirmed the stability of interactions between the top drugs and the protein. In conclusion, we have discovered promising drugs that can potentially control the monkeypox virus and should be further explored through experimental assays and clinical trials to assess their actual activity against the disease. The findings of this study could lay the foundation for screening repurposed compounds as possible antiviral treatments against various highly pathogenic viruses., Competing Interests: Conflict of interestThe authors declared that they have no conflicts of interest in this work., (© The Author(s), under exclusive licence to Indian Virological Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Edible bird's nest (EBN) is made up of sialylated-mucin glycoprotein with various health benefits due to its high antioxidative activity. However, as a macromolecule with distinct charged sialic acid and amino acids, fractions with different charges would have varied physicochemical properties and antioxidant activity, which have not been studied. Therefore, this study aimed to fractionate and purify the enzymatic hydrolysed of cleaned EBN (EBNh c ) and EBN by-product (EBNh byp ) through anion exchange chromatography (AEC), and determine their molecular weights, physicochemical properties, and antioxidative activities. Overall, 26 fractionates were collected from enzymatic hydrolysate by AEC, which were classified into 5 fractions. It was found that the positively charged fraction of EBNh c (CF 1) and EBNh byp (DF 1) showed the significantly highest (p < 0.05) soluble protein contents (22.86 and 18.40 mg/g), total peptide contents (511.13 and 800.47 mg/g) and ferric reducing antioxidant power (17.44 and 6.96 mg/g) among the fractionates. In conclusion, a positively charged fraction (CF 1 and DF 1) showed more desired physicochemical properties and antioxidative activities. This research suggests the potential of AEC fractionation as a technology to purify EBN and produce positively charged EBN fractionates with antioxidative potential that could be applied as food components to provide health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Microplastic (MP) pollution poses a global concern, especially for benthic invertebrates. This one-month study investigated the accumulation of small MP polymers (polypropylene and polyester resin, 3-500 μm, 250 μg L -1 ) in benthic invertebrates and on one alga species. Results revealed species-specific preferences for MP size and type, driven by ingestion, adhesion, or avoidance behaviours. Polyester resin accumulated in Mytilus galloprovincialis, Chamelea gallina, Hexaplex trunculus, and Paranemonia cinerea, while polypropylene accumulated on Ulva rigida. Over time, MP accumulation decreased in count but not size, averaging 6.2 ± 5.0 particles per individual after a month. MP were mainly found inside of the organisms, especially in the gut, gills, and gonads and externally adherent MP ranged from 11 to 35 % of the total. Biochemical energy assessments after two weeks of MP exposure indicated energy gains for water column species but energy loss for sediment-associated species, highlighting the susceptibility of infaunal benthic communities to MP contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii , exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A ( 1 ) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy ( E max ) and potency (EC 50 ) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1 . Molecular dynamics simulation of a tetrameric 44 -bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.

The construction industry's rapid growth poses challenges tied to raw material depletion and increased greenhouse gas emissions. To address this, alternative materials like agricultural residues are gaining prominence due to their potential to reduce carbon emissions and waste generation. In this context this research optimizes the use of banana leaves ash as a partial cement substitution, focusing on durability, and identifying the ideal cement-to-ash ratio for sustainable concrete. For this purpose, concrete mixes were prepared with BLA replacing cement partially in different proportions i.e. (0 %, 5 %, 10 %, 15 %, & 20 %) and were analyzed for their physical, mechanical and Durability (Acid and Sulphate resistance) properties. Compressive strength, acid resistance and sulphate resistance testing continued for 90 days with the intervals of 7, 28 and 90 days. The results revealed that up to 10 % incorporation of BLA improved compressive strength by 10 %, while higher BLA proportions (up to 20 %) displayed superior performance in durability tests as compared to the conventional mix. The results reveal the potentials of banana leave ash to refine the concrete matrix by formation of addition C-S-H gel which leads towards a better performance specially in terms of durability aspect. Hence, banana leaf ash (BLA) is an efficient concrete ingredient, particularly up to 10 % of the mix. Beyond this threshold, it's still suitable for applications where extreme strength isn't the primary concern, because there may be a slight reduction in compressive strength., Competing Interests: 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., (© 2024 The Authors.)

Background: Early pregnancy nutritional status can be associated with adverse birth outcomes such as small-for-gestational age (SGA) and low birth weight (LBW). BMI (Body Mass Index) and MUAC (Mid-upper arm circumference) are easy to use assessments and are indicative of the pre-pregnancy nutritional status if obtained in the first trimester. This study primarily assesses the association of maternal nutritional status using BMI and MUAC with SGA in a community-based cohort of Pakistani women. It also aims to determine the predictive ability of MUAC and BMI in predicting SGA. Secondarily, we assessed the association between maternal nutrition and large for gestational age (LGA) and LBW., Methods: This study is a secondary analysis of an ongoing pregnancy cohort "Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA)"in Ibrahim Hyderi and Rehri Goth, Karachi. PRISMA participants who were enrolled between January 2021 to August 2022 were included given they had a gestational age < 14 weeks confirmed via ultrasound, MUAC and BMI measurements were available and birth weight was captured within 72 hours. Multivariable logistic regression was used to determine an association between maternal nutritional status and SGA. The PRISMA study was approved by the Aga Khan University Ethics Review Committee (2021-5920-15,518)., Results: Of 926 women included in the analysis, 26.6% (n = 247) had a low MUAC (< 23 cm) while 18.4% (n = 171) were underweight (BMI < 18.5 kg/m2). Nearly one third of low MUAC and underweight women delivered SGA infants (34.4 and 35.1% respectively). Underweight women and women with low MUAC had a statistically significant association with SGA (Underweight: OR 1.49, 95% CI 1.1,2.4; Low MUAC-OR 1.64, 95% CI 1.2,2.3) as well as LBW (Underweight: OR-1.63, 95% CI 1.1,2.4; Low MUAC-OR-1.63, 95% CI 1.2,2.3). ROC curves showed that MUAC and BMI had modest predictability for SGA (AUC < 0.7)., Conclusion: Maternal nutritional status as indicated by BMI and MUAC are strongly associated with adverse pregnancy outcomes including SGA, LGA and LBW. Although MUAC and BMI are widely used to determine maternal nutritional status, they have poor predictive ability for newborn size. Further research is needed to identify other tools or a combination of tools to better predict adverse birth outcomes in resource-limited settings and plan interventions., (© 2024. The Author(s).)

Smart functional materials with captivating optical properties are of immense importance due to their versatile applicability in anticounterfeiting and forensic science. A fluorene-naphthalene Schiff base (FNH) that displays aggregation induced emission, mechanofluorochromism and excitation wavelength dependent fluorescence inherent to the pristine and ground samples is synthesized. Water/solvent-based invisible security inks for flexo/screen printing were formulated using FNH as a smart pigment to check the originality of documents/branded products etc. The prints with good photostability, adherence to substrate and rub resistance are invisible in daylight showcasing multiple non-destructive and destructive techniques to authenticate the document. The inked area on UV dull paper substrate exhibits a weak emission, which is observed by the forger under UVA light. However, the user can validate the authenticity of the document by rubbing the print with hard objects, especially using a metal coin or glass rod to perceive a human eye detectable intensification in the orange fluorescence under the same illumination source. The intensity of the orange fluorescence reverts to the original, which enables the reuse of the security document after originality check. Yet another nondestructive authentication method is to observe a cyan fluorescence from the print and orangish yellow fluorescence from the rubbed printed region when shined with a 270-400 nm light source, whereas a cyanish green fluorescence both from the unrubbed and rubbed regions of the print when illuminated with a visible light source ranging from 420 to 480 nm. An additional verification through a destructive technique is to perceive red and yellow fluorescence of the ink film upon contact with THF and NaOH/KOH, respectively and a penetrating red fluorescence from the rear side of the THF-exposed printed area of the paper. The multi-level security features that cannot be easily replicated by the forger but allows a simple and easy validation process by the user are unique to FNH, used as a single pigment in the inks. Further, the applicability of the ground FNH in forensic science is established to distinctly observe Level I to II details of latent fingerprints., 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 Elsevier Inc. All rights reserved.)

Introduction: Needlestick injuries (NSIs) represent a significant source of bloodborne viruses in the healthcare sector, particularly in dentistry. Developing effective infection control programs necessitates access to surveillance data. A comprehensive evaluation, encompassing human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and serological testing, is crucial due to the potential lack of immediate symptoms in infected patients. It is essential to verify hepatitis B and tetanus immunization statuses and seek guidance from infectious disease experts for post-exposure prophylaxis. Aim and objective: This study aims to assess the knowledge, attitudes, and perceptions of NSIs among dentistry students in Riyadh, Saudi Arabia., Methods: Conducted during the 2023-2024 academic year in Riyadh, Saudi Arabia, this cross-sectional study evaluated the knowledge, attitudes, and perceptions of undergraduate dental medicine students regarding NSIs. Ethical approval was obtained, and informed consent was meticulously collected. Before participation, potential subjects were furnished with a comprehensive information sheet outlining the study's purpose, the survey's nature, expected duration, and potential risks or benefits. The document emphasized their unequivocal right to withdraw from the study at any point without any adverse consequences. Data collection relied on an online survey administered to third and final-year dental students selected from specific universities. This selection criterion ensured that participants were directly relevant to the dental education context under investigation. Careful exclusions were made to minimize potential bias, particularly by excluding students from academic years other than the third and final years, thus maintaining a specific focus on this subgroup. Data analysis primarily compared NSI occurrences and awareness based on dental college and academic year. Detailed findings are presented in the results section., Results: The study unveiled high vaccination rates (95.23%) and significant levels of education regarding bloodborne infections (81.38%) among participants. However, it was noteworthy that 72.72% believed their vaccinations offered complete protection. Only 47.18% believed that wearing surgical gloves reduced the risk of NSIs, while a substantial majority (93.07%) opposed the practice of needle recapping. Moreover, 76.19% demonstrated knowledge of post-exposure prophylaxis, indicating room for improvement in healthcare safety practices. Statistical analysis identified significant associations between the Dental College attended and both NSI occurrence (χ²=12.164, p=0.058) and awareness (χ²=14.629, p=0.023). Conversely, the academic year exhibited no significant relationship with either NSI occurrence (χ²=1.2, p=0.55) or awareness (χ²=0.44, p=0.8). Additionally, the study revealed non-normal distributions for both NSI occurrence (p<0.001) and awareness (p<0.001) among participants., Conclusion: In conclusion, this study underscores the pivotal role of awareness in mitigating NSI occurrences among dental students. Irrespective of their academic year, heightened awareness significantly correlated with reduced NSI incidence. These findings bear significant implications for dental education and practice, emphasizing the imperative need for comprehensive education and awareness initiatives to bolster healthcare safety among dental professionals., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Thekkiniyakath Ali et al.)

The International Agency for Research on Cancer has unequivocally classified inorganic arsenic as a Group 1 carcinogen, definitively establishing its potential to induce cancer in humans. Paradoxically, despite its well-documented toxicity, arsenic finds utility as a chemotherapeutic agent. Notable examples include melarsoprol and arsenic trioxide, both employed in the treatment of acute promyelocytic leukemia. In both therapeutic and hazardous contexts, arsenic can accumulate within cellular environments, where it engages in intricate interactions with protein molecules. Gaining a comprehensive understanding of how arsenic compounds interact with proteins holds immense promise for the development of innovative inhibitors and pharmaceutical agents. These advancements could prove invaluable in addressing a spectrum of arsenic-related diseases. In pursuit of this knowledge, we undertook a systematic exploration of the Protein Data Bank, with a focus on 902 proteins intricately associated with 26 arsenic compounds. Our comprehensive investigation reveals insights into the interactions between these arsenical compounds and amino acids located within a 4.0 Å molecular distance from arsenic-binding sites. Our findings identify that cysteine, glutamic acid, aspartic acid, serine, and arginine frequently engage with arsenic. In complement to our computational analyses, we conducted rigorous Raman spectroscopy studies on the top five amino acids displaying robust interactions with arsenic. The results derived from experimental Raman spectroscopy were meticulously compared with our computational assessments, thereby enhancing the reliability and depth of our investigations. The current study presents a multidimensional exploration into the elaborate interplay between arsenic compounds and proteins. By elucidating the specific amino acids that preferentially interact with arsenic, this study not only contributes to the fundamental understanding of these molecular associations but also lays the foundation for future endeavors in drug design and therapeutic interventions targeting arsenic-related illnesses. Our work at the convergence of toxicology, medicine, and molecular biology carries profound implications for advancing our knowledge of arsenic's dual nature as both a poison and a potential cure., Competing Interests: The authors assert that they have not received any remuneration from commercial organizations or industries for conducting this research., (This journal is © The Royal Society of Chemistry.)

Introduction: Severe COVID-19 is associated with a dysregulated immune response that usually leads to cytokine release syndrome. This study aimed to compare the use of extracorporeal blood purification therapy (Oxiris ® ) versus standard continuous renal replacement therapy (CRRT) in critically-ill patients with severe COVID-19., Methods: This was a national, multicenter, retrospective study of patients with COVID-19 admitted to the intensive care unit (ICU) between March and October 2020 who required CRRT. Patients were categorized into two groups: Oxiris ® CRRT and standard CRRT. The primary outcome was the number of patients alive and ventilator-free at 30-days post-CRRT treatment. Key secondary endpoints included change in inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and PaO 2 /FiO 2 ratio at 24- and 72-h post Oxiris ® initiation., Results: Thirty-five patients received Oxiris ® CRRT and 23 patients received standard CRRT. The primary outcome was 31.4% in the Oxiris ® group versus 4.3% in the standard CRRT group (adjusted odds ratio 5.97, 95% confidence interval [CI], 0.64-55.6; p  = 0.117). In the Oxiris ® group, interleukin-6 (IL-6) concentrations significantly decreased at 24 and 72-h ( p  = 0.033) and PaO 2 /FiO 2 ratio significantly increased at 24 and 72 h after Oxiris ® initiation ( p  = 0.001). There was no significant change in SOFA scores at 24- and 72-h after Oxiris ® initiation., Conclusion: The number of patients alive and ventilator-free at 30-days was higher in the Oxiris ® group than that in the standard CRRT group; however, the difference did not reach statistical significance after adjusting for the baseline severity of illness. There was a significant reduction in IL-6 and significant improvement in PaO 2 /FiO 2 ratio after Oxiris ® CRRT initiation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF., Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses., Results: A total of 998 reports from 499 children with T1D aged 8 to 18 years (study = 276, control = 223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children's care during lockdown ( P  = .019). Patients had better compliance with treatment ( P  = .002), a reversed sleep pattern ( P  = .033), increased food intake ( P  ⩽ .001), and less exercise ( P  < .001). Children and parents perceived better QoL during lockdown ( P  ⩽.001) with no differences between their reports in "Diabetes Symptoms", "Treatment Adherence," and "Communication" domains. Self and proxy reports were different in all domains during non-lockdown ( P  = <.001-.009). In gap analysis, although not statistically significant, the gap was approximated between children's and parents' perceptions in all domains during lockdown., Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction Procedural sedation is a common procedure conducted in emergency departments (ED) across the world, which requires patients to receive anesthesia/sedation medication in a controlled environment in order to alleviate pain, anxiety, and suffering, thereby allowing multiple procedures to be completed in a safe and timely manner. We deploy this technique for joint reductions, burns dressings, wound repairs, etc. in our ED. As a large tertiary referral hospital ED, we aimed to benchmark our practice for this high-acuity procedure against international standards. The main objective of our audit was to benchmark our current practice of procedural sedation against international standards from the Royal College of Emergency Medicine (RCEM), United Kingdom, and American College of Emergency Physicians (ACEP) guidelines. As a secondary objective, we aimed to design and implement a multi-lingual procedural sedation leaflet for our patients and their carers. Methods A retrospective electronic healthcare records review was conducted from January 2019 to August 2022 following which a convenience sample of 100 patients was selected. Records audited were obtained from the Hospital Quality and Pharmacy departments. We selected patients from the data provided by selecting sedation medication used (ketamine, midazolam, propofol) and frequency documented as 'pre-procedure' (Pre-Proc). We included patients of all age groups who received procedural sedation in the emergency department and excluded inpatient encounters. After reviewing RCEM and ACEP guidance, we studied 14 criteria and standards. A team comprising physicians and hospital interpreters was set up to draft a procedural sedation leaflet. After hospital marketing team approval, these were published in Arabic, English, Urdu, Hindi, Bengali, and Malayalam. Results Compliance percentages of the 14 criteria were calculated. A "traffic light" color scheme was used to inform the reader of areas of good practice and areas for improvement. Percentages of 90-100% (green) were considered compliant, 80-89% (amber) were partially compliant, and 79% or less (red) were non-compliant. Of the 14 criteria, 10 were fully compliant. One criterion was partially compliant and three criteria were non-compliant. Conclusion Overall, we performed well in in this audit with 100% compliance rates in many areas. We identified that we had no written discharge information leaflet for our patients and carers. We drafted a multi-lingual procedural sedation leaflet and stocked this in the department. Through face-to-face education, we re-trained physicians on the importance of documentation when adhering to safe practices around procedural sedation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khamis AlBedwawi et al.)

This study aims to determine the effects of various alkaline pHs on the nutritional and functional properties of protein isolated from defatted chia flour (DCF). The DCF isolated using alkali extraction method at pH 8.5, 10.0, and 12.0 were coded as CPI-8.5, CPI-10.0, and CPI-12.0, respectively. The highest extraction yield and protein recovery yield was demonstrated by CPI-12.0 (19.10 and 59.63%, respectively), with a total protein content of 74.53%, and glutelin showed the highest portion (79.95%). The CPI-12.0 also demonstrated the most elevated essential (36.87%), hydrophobic (33.81%), and aromatic (15.54%) amino acid content among other samples. The DCF exhibited the highest water (23.90 gg -1 ) and oil (8.23 gg -1 ) absorption capacity, whereas the CPI-8.5 showed the highest protein solubility (72.31%) at pH 11. DCF demonstrated the highest emulsifying capacity at pH 11 (82.13%), but the highest stability was shown at pH 5 (82.05%). Furthermore, CPI-12.0 at pH 11 shows the highest foaming capacity (83.16%) and stability (83.10%). Despite that, the CPI-10.0 manifested the highest antioxidant capacity (DPPH: 42.48%; ABTS: 66.23%; FRAP: 0.19), as well as ACE-I (35.67%). Overall, the extraction pH had significant effects in producing chia protein isolates (CPI) with improved nutritional and functional qualities.

Environmental variation is the most crucial problem as it is causing food insecurity and negatively impacts food availability, utilization, assessment, and stability. Wheat is the largest and extensively cultivated staple food crop for fulfilling global food requirements. Abiotic stresses including salinity, heavy metal toxicity, drought, extreme temperatures, and oxidative stresses being the primary cause of productivity loss are a serious threat to agronomy. Cold stress is a foremost ecological constraint that is extremely influencing plant development, and yield. It is extremely hampering the propagative development of plant life. The structure and function of plant cells depend on the cell's immune system. The stresses due to cold, affect fluid in the plasma membrane and change it into crystals or a solid gel phase. Plants being sessile in nature have evolved progressive systems that permit them to acclimatize the cold stress at the physiological as well as molecular levels. The phenomenon of acclimatisation of plants to cold stress has been investigated for the last 10 years. Studying cold tolerance is critical for extending the adaptability zones of perennial grasses. In the present review, we have elaborated the current improvement of cold tolerance in plants from molecular and physiological viewpoints, such as hormones, the role of the posttranscriptional gene, micro RNAs, ICE-CBF-COR signaling route in cold acclimatization and how they are stimulating the expression of underlying genes encoding osmoregulatory elements and strategies to improve cold tolerance in wheat., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The world has faced unprecedented disruptions like global quarantine and the COVID-19 pandemic due to SARS-CoV-2. To combat these unsettling situations, several effective vaccines have been developed and are currently being used. However, the emergence of new variants due to the high mutation rate of SARS-CoV-2 challenges the efficacy of existing vaccines and has highlighted the need for novel vaccines that will be effective against various SARS-CoV-2 variants. In this study, we exploited the four structural proteins of SARS-CoV-2 to execute a potential multi-epitope vaccine against SARS-CoV-2 and its variants. The vaccine was designed by utilizing the antigenic, non-toxic, and non-allergenic B-cell and T-cell epitopes, which were selected from conserved regions of viral proteins. To build a vaccine construct, epitopes were connected through different linkers and an adjuvant was also attached at the start of the construct to enhance the immunogenicity and specificity of the epitopes. The vaccine construct was then screened through the aforementioned filters and it scored 0.6019 against the threshold of 0.4 on VexiJen 2.0 which validates its antigenicity. Toll-like receptors (i.e., TLR2, TLR3, TLR4, TLR5, and TLR8) and vaccine construct were docked by Cluspro 2.0, and TLR8 showed strong interaction with construct having a maximum negative binding energy of - 1577.1 kCal/mole. C-IMMSIM's immune simulations over three doses of the vaccine and iMODS' molecular dynamic simulations were executed to assess the reliability of the docked complexes. The stability of the vaccine construct was evaluated through the physicochemical analyses and the findings suggested that the manufactured vaccine is stable under a wide range of circumstances and can trigger immune responses against various SARS-CoV-2 variants (due to conserved epitopes). However, to strengthen the formulation of the vaccine and assess its safety and effectiveness, additional investigations and studies are required to support the computational data of this research at in-vitro and in-vivo levels., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00156-2., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Moringa oleifera (MO) phytochemicals and therapeutic properties improve hyperglycemia and treat type 2 diabetes. Thus, this study examined the effects of MO leaf capsules on blood glucose management in type 2 diabetic mellitus (T2DM) and hypertension and their safety. A prospective placebo-controlled experiment randomly assigned 24 patients to receive 3g and 6g of MO leaf capsules twice a day or a placebo for three months. Pre- and post-study lab and clinical outcomes were assessed. The placebo control group and 3g MO leaf showed a minor change, whereas 6g and control placebo showed a considerable drop in examined features. MO usage was safe. In T2DM patients, MO leaves lowered blood pressure, requiring further study. MO leaves may help T2DM patients manage blood pressure and blood sugar, according to the study. MO's therapeutic components need more research.

The advancement in the internet of things (IoT) technologies has made it possible to control and monitor electronic devices at home with just the touch of a button. This has made people lead much more comfortable lifestyles. Elderly people and those with disabilities have especially benefited from voice-assisted home automation systems that allow them to control their devices with simple voice commands. However, the widespread use of cloud-based services in these systems, such as those offered by Google and Amazon, has made them vulnerable to cyber-attacks. To ensure the proper functioning of these systems, a stable internet connection and a secure environment free from cyber-attacks are required. However, the quality of the internet is often low in developing countries, which makes it difficult to access the services these systems offer. Additionally, the lack of localization in voice assistants prevents people from using voice-assisted home automation systems in these countries. To address these challenges, this research proposes an offline home automation system. Since the internet and cloud services are not required for an offline system, it can perform its essential functions, while ensuring protection against cyber-attacks and can provide quick responses. It offers additional features, such as power usage tracking and the optimization of linked devices.

Background: Self-medication (SM) has many potential drawbacks, including toxicity, drug resistance, severe adverse effects, drug interactions, drug abuse, and drug dependence, but it is still widely used for a variety of reasons, including time and money savings, symptom prevention or treatment of minor illnesses, a lack of access to doctors, etc. This study aimed to describe and analyse the usage of antibiotics without a prescription, self-medication practises, and patterns of using them among Saudis., Materials and Methods: In 13 provinces of Saudi Arabia, a community-based cross-sectional study was done. After gaining consent, data were gathered from 420 adults during face-to-face interviews using a questionnaire. SPSS was used to analyse the data once it had been entered into Microsoft Excel (Microsoft® Corp., Redmond, WA)., Results: Regarding self-medication, among 208 participants, there was a male predominance and among upper lower class with respect to socioeconomic status. The self-medication rate was found to be higher among graduates and professionals with respect to education and occupation. Self-medication was discovered to be more prevalent among metropolitan residents. The majority of those who started using self-medication got their knowledge from various advertisements. The most frequent symptom of self-medication was fever, followed by a common cold. The most commonly used medication was paracetamol, followed by cough syrups. Weight loss advertisements influence participants the most for self-medication, followed by hair loss and diabetes. TV advertisements have the highest influence on people practising self-medication., Conclusion: The study calls for greater knowledge of the impacts of antibiotic self-medication, which can be accomplished through efficient measures including behaviour change communication and encouraging more research into its causes and effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Thekkiniyakath Ali et al.)

With global urbanization on the increase and cities now hosting more than half of the planet's population, there are concerns regarding the protection of urban commons as part of sustainability efforts, especially in sub-Saharan Africa. Decentralized urban planning is a policy tool and practice that is used to organize urban infrastructure for sustainable development. Yet, how it can be used to sustain the urban commons remains fragmented in the literature. This study reviews and synthesizes urban planning and urban commons literature using the Institutional Analysis and Development Framework and the non-cooperative game theory to identify how urban planning can protect and sustain the urban commons - green commons, land commons, and water commons - in Ghana. The study, based on the determination of different theoretical scenarios for the urban commons, identified that decentralized urban planning can help sustain the urban commons, but it is operationalized in an unfavorable political environment. For green commons, there are competing interests and poor coordination amongst planning institutions, and the absence of self-organizing bodies in managing the use of such resources. For land commons, increased land litigations are characterized by corruption and poor management of land cases in the formal land courts, and despite the existence of self-organizing institutions, these institutions have failed to act responsibly to protect land commons due to the increasing demands and values (profitability) of lands in urban areas. For water commons, urban planning has not been fully decentralized and there is also the absence of self-organizing bodies in urban water use and management. This is coupled with the waning of customary water protection provisions in urban centers. Based on the findings, the study generally proposes institutional strengthening as the bedrock for enhancing the sustainability of the urban commons through urban planning and should therefore be of policy focus moving forward., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors.)

Abstract: Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods : This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 μg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. The primary outcome was in-hospital mortality at 60 days or at discharge, whichever occurred first. Secondary outcomes included time to death, change in Sequential Organ Failure Assessment (SOFA) score at 72 h of randomization, intensive care unit length of stay, hospital length of stay, and vasopressor duration. Results: A total of 106 patients (53 in each group) were enrolled in this study. The study was terminated early because of a lack of funding. The median baseline SOFA score was 10 (interquartile range, 8-12). The primary outcomes were similar between the two groups (triple therapy, 28.3% vs. control, 35.8%; P = 0.41). Vasopressor duration among the survivors was similar between the two groups (triple therapy, 50 h vs. control, 58 h; P = 0.44). Other secondary and safety endpoints were similar between the two groups. Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Purpose: This study sought to assess the prevalence of thrombocytopenia (TCP), underlying aetiologies of chronic liver disease, and the grading and prognostic systems for chronic liver disease (CLD) using non-invasive biomarkers: the Fibrosis index and the Model for End-Stage Liver Disease-Na (MELD-Na) Score, respectively., Patients and Methods: This was a 15-month multi-centric cross-sectional study of 105 patients with chronic liver disease (CLD). The study was conducted using Sept 2019 to Nov 2020 admission records of CLD patients from Ma'abar City in Dhamar Governorate, Yemen., Results: A total of 63 (60%) and 42 (40%) patients were identified as thrombocytopenic and non-thrombocytopenic, respectively. The means ± SD of the MELD score and FI were 19 ± 7.302 and 4.1 ± 1.06. TCP prevalence among leukopenic and non-leukopenic patients was 89.5% and 53.5%, respectively (P = 0.004). Likewise, the prevalence of traditional-ultrasonography-diagnosed cirrhotic patients needing liver transplantation (LT) was 82.3% versus 61.3% among corresponding non-cirrhotic patients (P = 0.000)., Conclusion: The prevalence of TCP among the participants of this study was similar to the global rate. However, the prevalence of decompensation was much higher among CLD patients than that found elsewhere, highlighting a need to improve methods for the early diagnosis of CLD in Yemen. This study also identified problems with the diagnostic work-up for non-infectious aetiologies of CLD. The findings suggest the need to improve clinician awareness about effective diagnostic strategies for these aetiologies., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Al-Dholae et al.)

Background: High resilience increases nurses' ability to cope with job-related stressors and enhances job satisfaction and, consequently, their retention. The study aims to identify resilience predictors and perceptions of transformational leadership in a convenience sample of registered nurses in Lebanon., Methods: An anonymous cross-sectional survey of a convenience sample of 240 registered nurses working for more than a year at three private hospitals in an underserved area in South Lebanon was used. The survey instrument included demographic questions, the True Resilience Scale ©, and the Global Transformational Leadership Scale. Multiple linear regression was used to assess the predictors of resilience after a descriptive analysis of the study variables., Results: The survey response rate was 85%. The nurses' mean resilience score was 119.4 (SD 15.3), and their perception of transformational leadership score was M = 25.0, SD = 6.8. Compared to bedside nurses, nurse managers, nurses with more than five years of experience, and nurses in critical nursing units had statistically significant higher resilience scores (p < 0.05). Resilience scores and perception of global transformational leadership were moderately correlated (r = 0.53, p < 0.05). In the final multiple linear regression model, 30% of the variation in resilience scores was explained by designation (p < 0.05) and perception of Global Transformational Leadership (p < 0.01). Perception of global transformational leadership scores explained 29% of the variance in resilience scores. Designation and perception of global transformational leadership predicted resilience in this sample., Conclusions: A national survey of the Lebanese nursing workforce is needed to achieve an improved predictive model and support policy developments to increase resilience among bedside nurses and retain them in the nursing workforce. Nurse administrators can help by strengthening their transformational leadership behaviors. Consistent use of transformational leadership styles will strengthen bedside nurses' resilience, increase nurse retention, and help sustain the Lebanese nursing workforce., (© 2023. The Author(s).)

A novel antibacterial immunostimulant using Platinum nanoparticles (PtNPs) and lectin from Metapenaeus dobsoni (Md-Lec) was developed. The Md-Lec and PtNPs (Pt-lec) hybrid formed through non-covalent interaction exhibits antimicrobial activity against fish specific pathogens by affecting membrane integrity and producing excess reactive oxygen species. The therapeutic efficacy of Pt-lec was demonstrated through rescuing Aeromonas hydrophila infected Nile Tilapia. Pt-lec prevents the infection spreading and reduces the bacterial bioburden in less than 12 h, and as a result of this the fish were restored to normalcy. To assess immunostimulation, we studied the expression of three different immune related genes, namely LEC, Myd88 and COX-2 in the gills, liver, spleen and kidney of fish under various experimental conditions. Our results showed that Pt-lec treatment appeared to be better when compared to lectin alone in enhancing the expression of Myd88 and COX-2, but LEC was not as expected. These results suggest that Pt-lec has the ability to protect Nile Tilapia against bacterial infection by restricting bacterial bioburden through their direct effects on the bacterial membrane and indirectly through their effects on host immune-related gene expression. This hybrid could have potential "green" application in fish farming in rescuing infected animals when compared to widely and unregulated antibiotics., (© 2023. The Author(s).)

This study evaluates the cytomorphometric measures of cells obtained from the buccal mucosa of dental students to assess the fluctuation of the cellular characteristics among relatively normal subjects, with any potential correlations with demographic information, different habits, and hormonal disturbance. This prospective study included 100 dental students with no detectable oral alterations submitted to brush cytology. The smears were fixed with 95% ethyl alcohol and stained with hematoxylin and eosin stain. The stained section was observed under an image analyzer for cytomorphometric analysis. Cytopathological observations were recorded, including inflammation, microbial colonies, micronuclei, keratinization, overlapping, and hemorrhage. Chi-square tests were applied for non-parametric variables. One-way analysis of variance (ANOVA) was used to compare the cytometric parameters to habits and hormonal disturbances. A p-value < 0.05 was considered statistically significant. The results showed close proximity among subjects in the matter of cytomorphometric measures; no significant influence of sex, smoking, alcohol drinking habits, and menstruation was found on cytomorphometric diameters or cytopathological observation, and vice versa, while polycystic ovary syndrome impacted nuclear and nuclear-cytoplasmic ratio (p = 0.003, p = 0.02), respectively. Oral exfoliative cytology combined with cytomorphometric analysis for the studied normal individuals can be helpful in various investigations of oral and systemic diseases.

Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins, CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation, and induces metabolic shift toward glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells. Interactions of CLIC proteins with structural components of the inner mitochondrial membrane offer mechanistic insights. Endothelial CLIC4 excision and mitofusin 2 supplementation have protective effects in human PAH cells and preclinical PAH. This study is the first to demonstrate the key role of endothelial intracellular chloride channels in the regulation of mitochondrial structure, biogenesis, and metabolic reprogramming in expression of the PAH phenotype.

The human toll-like receptor ( hTLR ) 4 single nucleotide polymorphisms (SNPs) are interconnected with cancer, multiple genetic disorders and other immune-related diseases. The detrimental effect of SNPs in hTLR 4 with respect to structure and function has not been explored in depth. The present study concatenates the biological consequences of the SNPs along with structural modifications predicted at the hTLR4 gene. A total of 7910 SNPs of hTLR4 were screened, and 21 damage-causing SNPs were identified. Out of 21, seven are present in the extracellular region, of which three were detected as deleterious and the fourth one as moderate. These three mutations are located in a highly conserved region and influence conformational change. The change leads to the widening of the Leucine-rich repeat (LRR) arc to a maximum of 16.9 Å and a minimum of 8.7 Å. Expansion/shortening of LRR arc, never discussed before, would cause loss of myeloid differentiation factor 2 (MD-2) interactions in the interior and diminish lipopolysaccharide (LPS) responses. Similarly, in all mutant structures, the binding region for HMGB1 and LPS is deflating or in an unsupportive conformation. Thus, SNPs affect the regular signaling cascade and might result in human sepsis, genetic disorders, cancer and other immunological related diseases.Communicated by Ramaswamy H. Sarma.

Smart grids and smart homes are getting people's attention in the modern era of smart cities. The advancements of smart technologies and smart grids have created challenges related to energy efficiency and production according to the future demand of clients. Machine learning, specifically neural network-based methods, remained successful in energy consumption prediction, but still, there are gaps due to uncertainty in the data and limitations of the algorithms. Research published in the literature has used small datasets and profiles of primarily single users; therefore, models have difficulties when applied to large datasets with profiles of different customers. Thus, a smart grid environment requires a model that handles consumption data from thousands of customers. The proposed model enhances the newly introduced method of Neural Basis Expansion Analysis for interpretable Time Series (N-BEATS) with a big dataset of energy consumption of 169 customers. Further, to validate the results of the proposed model, a performance comparison has been carried out with the Long Short Term Memory (LSTM), Blocked LSTM, Gated Recurrent Units (GRU), Blocked GRU and Temporal Convolutional Network (TCN). The proposed interpretable model improves the prediction accuracy on the big dataset containing energy consumption profiles of multiple customers. Incorporating covariates into the model improved accuracy by learning past and future energy consumption patterns. Based on a large dataset, the proposed model performed better for daily, weekly, and monthly energy consumption predictions. The forecasting accuracy of the N-BEATS interpretable model for 1-day-ahead energy consumption with "day as covariates" remained better than the 1, 2, 3, and 4-week scenarios., (© 2022. The Author(s).)

The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research. Here, we integrate structural bioinformatics and experimental research approaches for the discovery and validation of small-molecule inhibitors of CLIC4. High-affinity allosteric binders were identified from a library of 1615 Food and Drug Administration (FDA)-approved drugs via a high-performance computing-powered blind-docking approach, resulting in the selection of amphotericin B and rapamycin. NMR assays confirmed the binding and conformational disruptive effects of both drugs while they also reversed stress-induced membrane translocation of CLIC4 and inhibited endothelial cell migration. Structural and dynamics simulation studies further revealed that the inhibitory mechanisms of these compounds were hinged on the allosteric modulation of the catalytic glutathione (GSH)-like site loop and the extended catalytic β loop which may elicit interference with the catalytic activities of CLIC4. Structure-based insights from this study provide the basis for the selective targeting of CLIC4 to treat the associated pathologies., Competing Interests: None., (Crown Copyright © 2023 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Diabetic Retinopathy affects one-third of all diabetic patients and may cause vision impairment. It has four stages of progression, i.e., mild non-proliferative, moderate non-proliferative, severe non-proliferative and proliferative Diabetic Retinopathy. The disease has no noticeable symptoms at early stages and may lead to chronic destruction, thus causing permanent blindness if not detected at an early stage. The proposed research provides deep learning frameworks for autonomous detection of Diabetic Retinopathy at an early stage using fundus images. The first framework consists of cascaded neural networks, spanned in three layers where each layer classifies data into two classes, one is the desired stage and the other output is passed to another classifier until the input image is classified as one of the stages. The second framework takes normalized, HSV and RGB fundus images as input to three Convolutional Neural Networks, and the resultant probabilistic vectors are averaged together to obtain the final output of the input image. Third framework used the Long Short Term Memory Module in CNN to emphasize the network in remembering information over a long time span. Proposed frameworks were tested and compared on the large-scale Kaggle fundus image dataset EYEPAC. The evaluations have shown that the second framework outperformed others and achieved an accuracy of 78.06% and 83.78% without and with augmentation, respectively.

P-glycoprotein (P-gp), a transmembrane glycoprotein, is mainly involved in lung cancer multidrug resistance. Several P-gp inhibitors have been developed to enhance the efficacy of chemotherapeutics and overcome drug resistance. However, most of them failed in the clinical stages due to undesirable side effects. Therefore, there is a requirement to develop P-gp inhibitors from natural sources. Dietary spice bioactives have been well-known for their anticancer activities. However, their role in modulating the P-gp activity has not been well investigated. Therefore, we have screened for the potential bioactives from various spice plants with P-gp modulatory activity using computational molecular docking analysis. The computational analysis revealed several key bioactives from curry leaves, specifically mahanimbine, exhibited a strong binding affinity with P-gp. Unfortunately, mahanimbine is available with few commercial sources at very high prices. Therefore, we prepared a curry leaves extract and isolated mahanimbine by a novel, yet simple, extraction method that requires less time and causes minimum environmental hazards. After purification, structure, and mass were confirmed for the isolated compound by IR spectrum and LC-MS/MS analysis, respectively. In the mechanistic study, hydrolysis of ATP and substrate efflux by P-gp are coupled. Hence, ATP binding at the ATPase-binding site is one of the fundamental steps for the P-gp efflux cycle. We found that mahanimbine demonstrated to stimulate P-gp ATPase activity. Concurrently, it enhanced the intracellular accumulation of P-gp substrates Rhodamine 123 and Hoechst stain, which indicates that mahanimbine modulates the function of P-gp. In addition, we have analyzed the complementary effect of mahanimbine with the chemotherapeutic drug gefitinib. We found that mahanimbine synergistically enhanced gefitinib efficiency by increasing its intracellular accumulation in lung cancer cells. Overall, mahanimbine has been shown to be a potent P-gp modulator. Therefore, mahanimbine can be further developed as a potential candidate to overcome chemoresistance in lung cancer., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Cereblon, an extensively studied multifunctional protein, is a Cullin 4-RING E3 ubiquitin ligase complex component. Cereblon is a well-known target of thalidomide and its derivatives. Cereblon is involved in multiple myeloma cell apoptosis. When ligands such as thalidomide and lenalidomide bind to cereblon, it recognizes various neosubstrates based on the ligand shape and properties. We have identified novel CRBN inhibitors, namely DHFO and its analogs, with structural features that are slightly different from thalidomide but stronger cereblon-binding affinity. We selected indanedione and indanone derivatives from the literature to understand and compare their cereblon-mediated substrate recognition potential., Methods: Computational investigations of possible CRBN inhibitors were investigated by molecular docking with Autodock Vina and DockThor programs. The properties of the compounds' ADME/T and drug-likeness were investigated. A molecular dynamics study was carried out for four selected molecules, and the molecular interactions were analyzed using PCA-based FEL methods. The binding affinity was calculated using the MM/PBSA method., Results: We conducted computational investigations on 68 indanedione and indanone derivatives binding with cereblon. Ten molecules showed better CRBN binding affinity than thalidomide. We studied the drug-likeness properties of the selected ten molecules, and four of the most promising molecules (DHFO, THOH, DIMS, and DTIN) were chosen for molecular dynamics studies. The MM/PBSA calculations showed that the DHFO, already shown to be a 5-LOX/COX2 inhibitor, has the highest binding affinity of - 163.16 kJ/mol with cereblon., Conclusion: The selected CRBN inhibitor DHFO has demonstrated the highest binding affinity with cereblon protein compared to other molecules. Thalidomide and its derivatives have a new substitute in the form of DHFO, which produces an interaction hotspot on the surface of the cereblon. Ease of chemical synthesis, low toxicity, versatile therapeutic options, and pleiotropism of DHFO analogs provide an opportunity for exploring clinical alternatives with versatile therapeutic potential for a new category of indanedione molecules as novel modulators of E3 ubiquitin ligases., Competing Interests: Declaration of Interest The authors declare no financial or personal relationships that are received for this work from any commercial institutions or industry. Conflict of Interest The writers affirm that they have received no compensation from commercial organizations or industries for this research work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Groundwater, is an alternative resource, is used as a supplement for irrigation as well as drinking purposes in Pakistan. This paper aims to determine the quantum and quality of groundwater in Matiari district of Sindh, Pakistan, through Electrical Resistivity Survey (ERS). The ERS was conducted at 52 location points using the ABEM Terrameter SAS 4000. The quantity of good quality groundwater has also been evaluated with ArcGIS interpolation techniques, i.e., the maximum percentage of fresh groundwater is 34% the marginal fresh groundwater 43% at the depth of with few patches of saline groundwater aquifers. Moreover, at 50-m depth, the percentage of fresh groundwater reduces to 21% and the marginal has increased to 48%. However, groundwater below the depth from 50 to 100 m was found only 8% fresh groundwater, 29% marginal, 49% salt water, and 14% high salt water. Analysis of groundwater samples for quality showed a good agreement with the quality obtained from VES results. In addition, a socio-economic survey of 55 tube well owners were conducted through interviews related to groundwater suitability and usage. According to the survey, about 62% of respondents are using good quality groundwater; however, 36% consuming the marginal and the remaining 2% are utilizing the hazardous quality of groundwater. The consumer satisfaction survey showed most farmers (89%) were satisfied with the groundwater usage, while 11% were unsatisfied due to poor-quality groundwater. The crop productivity could be enhanced through awareness and conjunctive use of marginal quality groundwater with the canal water., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Plant essential oils (EOs), which are acknowledged as generally recognized as safe (GRAS) by the Food and Drug Administration (FDA), have the potential to be used as a flavoring agent. However, there are limitations to some EOs, such as low water solubility and high volatility, which limit their application in food technology. This study was conducted to develop onion ( Allium cepa ) EO as a flavoring agent and determine its stability against environmental stress via an emulsification technique, with different concentrations of sodium caseinate, as a delivery system. Emulsions containing onion EO were prepared using different concentrations of sodium caseinate (3, 5, and 7% w / w ) via the solvent-displacement technique. The physical properties (average droplet size, color, turbidity, and stability measurement) and antibacterial activity (agar disk diffusion method) of emulsions were then determined. Results show that emulsion with 7% ( w / w ) sodium caseinate was the most desirable sample in terms of physical properties and antibacterial activity. Hence, it was selected for environmental stress studies (i.e., thermal processing, freeze-thaw cycles, and ultraviolet (UV) exposure). Results revealed that all types of environmental stresses had significant ( p < 0.05) effects on droplet size, color, turbidity, and stability. Generally, the environmental stresses increased the droplet size except in the freeze-thaw cycle case, while all stresses decreased the stability and lightness. All types of environmental stress treatment did not show a significant ( p < 0.05) effect on antibacterial activity enhancement against Salmonella Typhimurium and Listeria monocytogenes except in the case of UV treatment against L. monocytogenes . Therefore, the present work has demonstrated the potential use of emulsion as an encapsulation and delivery system of EO flavors for food applications., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Elham Taghavi et al.)

The Corona virus infection started at the end of 2019 in Wuhan - China and spread rapidly throughout the world, generating the Covid 19 pandemic. The manifestations of the Covid disease were extremely varied, from a simple flu, with fever, cough, weakness, headache, joint pain, up to severe pneumonia, with severe acute respiratory syndrome (SARS-Cov2) and even death. The symptomatology of the disease, the evolution and the complications that appeared varied, depending on the associated pathology - diabetes mellitus (DM), hypertension (HT), the age and the immune status of the patient. Aim: The ocular manifestations related to Covid 19 were mostly represented by conjunctivitis, but the neurotropic character of Corona virus could justify the appearance of certain neuro-ophthalmological manifestations, such as: optic neuritis (ON), cranial nerve palsies, visual field (VF) anomalies. The aim of this paper was to research the cases of optic neuropathy post-Covid 19, published in the specialty literature between 2020 and 2022. The following were evaluated: risk factors, distribution by age group and gender, evolution and complications, as well as the clinical forms of optic neuropathies. Materials and methods: We used Google Scholar and PubMed databases to find articles on optic neuropathies related to the Covid-19 infection. We followed the articles published during the pandemic and selected 21 cases, belonging to 17 authors, irrespective of their origin and the language in which they were written. Results: 21 patients affected by ON in the Covid-19 disease, 11 women and 10 men, were mentioned. The optic neuropathies described by the authors were: retrobulbar optic neuropathy, only one associated with myelin oligodendrocyte glycoprotein (MOG), papillitis, neuroretinitis, anterior ischemic optic neuropathy (AION), out of which one arteritic anterior ischemic optic neuropathy (AAION) and the others non-arteritic anterior ischemic optic neuropathy (NAAION), one being related to pronation in an oro-tracheal intubated (OTI) patient with acute respiratory distress syndrome (ARDS). Discussions: The neuro-ophthalmological complications associated with Covid 19 disease can be severe, so the patients should be monitored continuously. Many investigations (serological, immunological and imaging exams) are necessary to exclude other etiologies of ON. Conclusions: A complete ophthalmological exam is mandatory for each patient diagnosed with Covid 19 disease, even if they have ocular manifestations or not. Abbreviations: SARS-Cov2 = severe acute respiratory syndrome; DM = Diabetes mellitus; HT = Hypertension; ON = Optic neuritis; VF = Visual field ; NS = Nervous system; CRP = C-reactive Protein; CL = cytokines; IL = interleukins; TNFɑ = tumor necrosis factor; CNS = central nervous system; ACE = angiotensin-converting enzyme; CRVO = central retinal vein occlusion; MOG = myelin oligodendrocyte glycoprotein; MOG-AD = myelin oligodendrocyte glycoprotein antibody disease; BBB = blood-brain barrier; ARDS = acute respiratory distress syndrome; IOP = intraocular pressure; CVP = central venous pressure; MSOF = multiple systems organ failure; AAION = arteritic anterior ischemic optic neuropathy; NAION = non-arteritic anterior ischemic optic neuropathy; AION = anterior ischemic optic neuropathy; OCT = optical coherence tomography; CT = computer tomography; AFG = angiofluorography; MRI = magnetic resonance imaging; ESR = erythrocyte sedimentation rate; RF = rheumatoid factor; ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; AQP4 = anti aquaporin 4; NMO = neuromyelitis optica; CSF = cerebrospinal fluid; OTI = oro-tracheal intubated; VA = visual acuity; ONTT = optic neuritis treatment trial; RNFL = retinal nerve fiber layer; ICU = intensive care unit; LE = left eye; RE = right eye; MS = multiple sclerosis; ICH = intracranial hypertension; BCVA = best correction visual acuity; LP = light perception; APD = afferent pupillary defect; BM = biomicroscopy; PDN = prednisone; MTX = methotrexate; MTPN = methylprednisolone; NSAID = non-steroidal anti-inflammatory drugs; CGL = cells ganglion layer; VEP = visual evoked potential; CF = counting fingers., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Background: General health check-ups are an important element of healthcare, as they are designed to detect diseases, thereby reducing morbidity and mortality. Recent studies have found that financial literacy promotes preventive healthcare usage and reduces risky health behaviors such as smoking, lack of exercise, and gambling. Based on this evidence, we hypothesize that financial literacy, as a rational decision-making tool, is positively associated with health check-up behavior in Japan., Methods: We extracted data on financial literacy, the main explanatory variable of this study, from the 2010 wave of the Preference Parameter Study (PPS) of Osaka University. Data on health check-up behavior as a dependent variable, along with control variables, were obtained from the 2011 PPS wave. Our sample focused on Japan's middle-aged working population (40-64 years), and we applied probit regressions to test our hypothesis., Results: Our final sample size was 2,208 participants after merging the two datasets. Descriptive statistics show that respondents had moderate financial literacy (mean = 0.62, SD = 0.33), low financial education (mean = 0.17, SD = 0.38), and low participation (mean = 31.75%, SD = 46.56%) in the health check-up. The probit regression analysis showed that financial literacy is insignificantly associated with health check-up behavior in Japan (coefficient = -0.0229; 95% CI: -0.2011-0.1551; p-value = 0.801). However, demographic factors such as being male (coefficient = -0.2299; 95% CI: -0.3649--0.0950; p-value = 0.001), older (coefficient = 0.0280; 95% CI: 0.0188 - 0.0371; p-value = 0.000), and married (coefficient = 0.3217; 95% CI: 0.0728 - 0.5705; p-value = 0.011), as well as risky health behavior such as smoking (coefficient = -0.2784; 95% CI: -0.4262--0.1305; p-value = 0.000) are significantly related to health check-up behavior., Conclusions: Our results suggest that financial literacy insignificantly motivates people to behave rationally and understand the value of health check-ups as a tool for sustainable health., (© 2022. The Author(s).)

The prolonged COVID-19 pandemic has exacerbated existing socioeconomic and health risk factors and added additional dimensions to the loneliness problem. Considering the temporal extension of COVID-19, which exposes people to various loneliness conditions, we examined the development of loneliness and changing risk factors based on age and gender. We used longitudinal data from Hiroshima University's nationwide survey in Japan, conducted before and during the pandemic, to categorize loneliness into three types: long-term (feeling of loneliness experienced both before and during the pandemic), post-pandemic (feeling of loneliness experienced throughout the whole pandemic period), and fresh (feeling of loneliness experienced only in the last year of the pandemic). Loneliness categorization is important because the prolonged existence of the COVID-19 pandemic has added additional dimensions to the loneliness problem, which existing studies rarely identify. As a result, the distinction between long-term and fresh loneliness remains unexplained. The weighted logit regression results revealed that many Japanese people have remained or became lonely during the pandemic and identified variations based on gender, age, and changes in socioeconomic and health characteristics. More precisely, almost 52% of the participants experienced long-term loneliness, while 8% of the participants experienced post-pandemic loneliness, and nearly 5% experienced fresh loneliness. Age and having children were associated with long-term loneliness; gender, age, leaving full-time employment, financial literacy, change in health status, and change in depression were associated with post-pandemic loneliness; and gender, having children, living in rural areas, change in household assets, financial literacy, changes in health status, and changes in depression were associated with fresh loneliness. These results indicated that long-term, post-pandemic, and fresh loneliness have distinct characteristics. The Japanese government should devise distinctive solutions for people suffering from varying loneliness before and during the pandemic rather than adopting a generalized approach.

The influence of smartphone use on increased risk of feeling lonely has been recognized as a global public health concern. However, it is unclear whether this influence has changed during the ongoing COVID-19 pandemic, during which smartphones have become a particularly important means of communication due to health safety measures restricting personal interactions. We used Hiroshima University's online survey data collected from 18-28 February 2022, to assess the impact of smartphone use on loneliness in Japan. The final sample included 2630 participants aged over 20 years, with loneliness measured using the UCLA scale and smartphone use calculated as the duration of usage in minutes/day. Weighted logit regression analysis was used to examine the association between smartphone use and loneliness, with other demographic, socioeconomic, and psychological characteristics as explanatory variables. Contrary to conventional evidence, our findings show that smartphone use mitigated the risk of loneliness during the pandemic. This was especially true among females under 65 years old. We found that age, subjective health status, future anxiety, and depression impacted this relationship. The findings of this study can help guide policymaking by showing the importance of providing adequate digital platforms to manage loneliness and mental health during times of isolation.

Objective: This study aimed to determine whether or not developmental potential impacts clinical outcomes, when good grade blastocysts from Days 5 and 6 were transferred in frozen embryo transfer (FET) cycles., Methods: 654 women, including 460 (70.33%) on Day 5 and 194 (29.66%) on Day 6 were analyzed, in which 905 Day-5 and 274 Day-6 blastocysts were transferred. Only grade AA, AB, BA, BB quality and expansion grade between 3-6 (Gardner grading system) blastocysts survived and were included., Results: The implantation rate was higher, 41.9% (379/905) in normal Day-5 compared to delayed Day-6 blastocyst transfers - 36.5% (100/274), but not significant (p=0.1). The clinical pregnancy rate was similar and not significant (p=0.4) in normal Day-5 (32.4%), compared to delayed Day-6 (35%). Miscarriage rates were higher in normal Day-5 (13.3%) compared to delayed Day-6 (6.3%) blastocyst transfers but were not significant (p=0.06). On the other hand, the biochemical pregnancy rate was significantly higher (p=0.001) in the delayed Day-6 blastocysts (16.7%) transfer group compared to patients with normal Day-5 (2.4%) blastocyst transfers. Two patients had ectopic pregnancies from the delayed Day-6 blastocyst transfer group. Live-Birth rates were significantly higher in Day-5 blastocysts compared to Day-6 (p=0.03)., Conclusions: The developmental potential of embryos should not be considered a negative influence on pregnancy outcomes, especially good grade blastocysts vitrified on Days 5 and 6. Fully expanded blastocysts on Day-5 are considered similar in terms of outcomes to delayed Day-6 blastocysts; however, live-birth rates are significantly higher in Day-5 blastocysts.

Auto-grading of short answer questions is considered a challenging problem in the processing of natural language. It requires a system to comprehend the free text answers to automatically assign a grade for a student answer compared to one or more model answers. This paper suggests an optimized deep learning model for grading short-answer questions automatically by using various sizes of datasets collected in the Science subject for students in seventh grade in Egypt. The proposed system is a hybrid approach that optimizes a deep learning technique called LSTM (Long Short Term Memory) with a recent optimization algorithm called a Grey Wolf Optimizer (GWO). The GWO is employed to optimize the LSTM by selecting the best dropout and recurrent dropout rates of LSTM hyperparameters rather than manual choice. Using GWO makes the LSTM model more generalized and can also avoid the problem of overfitting in forecasting the students' scores to improve the learning process and save instructors' time and effort. The model's performance is measured in terms of the Root Mean Squared Error (RMSE), the Pearson correlation coefficient, and R-Square. According to the simulation results, the hybrid GWO with the LSTM model ensured the best performance and outperformed the classical LSTM model and other compared models such that it had the highest Pearson correlation coefficient value, the lowest RMSE value, and the best R square value in all experiments, but higher training time than the traditional deep learning model., Competing Interests: The authors have declared that no competing interests exist.

The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl- efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion. Biophysical assays confirmed specific binding to Zn2+, inducing membrane association and enhancing Cl- efflux in a pH-dependent manner. Together, our results identify a two-step mechanism with Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion, followed by pH-mediated activation of Cl- efflux., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)