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Electronic and structural properties of calcium clusters with a varying size range of 2–20 atoms are studied using a two-step scheme within the GW and density functional theory (DFT) with generalized gradient approximation (GGA). The GGA overestimates the binding energies, optimized geometries, electron affinities, and ionization potentials reported in the benchmark. The ground-state structure geometry and binding energy were obtained from the DFT for the ground-state structure of each cluster. The binding energy of the neutral clusters of the calcium series follows an increasing trend, except for a few stable even and odd clusters. The electronic properties of the calcium cluster were studied with an all-electron FHI-aims code. In the G0W0 calculation, the magic cluster Ca10 has relatively high ionization potential and low electron affinity. The obtained ionization potentials from the G0W0@PBE calculation showed that the larger cluster has less variation, whereas the electron affinities of the series have an increasing trend. The ionization potentials from the G0W0 benchmark for the calcium cluster series have not yet been described in the literature.

Abstract Background Policy research aims to provide evidence to inform government policy decisions about health and social care. Engaging and involving the public and patients in this work is widely recognised as essential. Research funders prioritise equality, diversity and inclusion (EDI) in patient and public involvement and engagement (PPIE), but people who are most likely to experience poor outcomes are also those least likely to be involved in research. This paper describes our experience of setting out to understand how to overcome barriers to EDI in PPIE in the research carried out by the National Institute for Health and Care Research (NIHR) Policy Research Unit in Maternal and Neonatal Health and Care (PRU-MNHC), in a PPIE consultation project we called The Listening Series. Methods We convened five video-recorded online discussion groups involving 20 individuals advocating for groups who are under-represented in our research. Those taking part included people working with Black and Asian women and families, young parents, those from socially deprived backgrounds, and women and families with physical and learning disabilities. Discussions focussed on practical solutions to addressing challenges to people being excluded, and how to improve EDI in our research. Learning and reflection Five key themes were identified: ‘build trust’; ‘involve us from the beginning’; ‘show us impact’; ‘use clear, appropriate and inclusive communication’; and ‘imagine life in our shoes’. We used the learning to create a guidance document for researchers and an accompanying 15-minute film. We also took practical steps to embed the learning strategically by expanding our Task Group for PPIE in the PRU-MNHC to include four Listening Series invitees with a remit to champion EDI in our research and ensure that it is embedded in our PPIE activities. We continue to reflect on and work to address the associated challenges. Conclusions The Listening Series helped us rethink our processes for inclusion to go beyond traditional methods of involvement and engagement. The themes identified pose challenges that require time, resource and empathic engagement from researchers to be meaningfully resolved. This has implications for policy makers and research funders who need to consider this in their processes.

This case report describes a 32-year-old Pakistani male patient with an Ewing sarcoma (ES) of the adrenal gland. Presenting complaints were abdominal distention, pain, low-grade fever, and weight loss. Initial studies, including imaging and tumor markers, ruled out any other possible origins of the mass. A percutaneous biopsy verified the tumor's neuroendocrine origin. Extensive involvement of nearby anatomical structures was discovered through exploratory laparotomy, rendering total resection difficult. Based on the presence of malignant, round, blue cells that were positive for specific immunostaining markers, the histopathology report supported the diagnosis of an ES with a staging of T3N0M0. Chemotherapy, in accordance with the VAC-IE protocol, was administered after debulking surgery. Subsequent imaging and close monitoring revealed no metastatic or residual tumors. Adrenal ES is an uncommon, aggressive tumor that mandates prompt diagnosis and management. This case report highlights the value of early detection and multimodal therapy in enhancing patient outcomes for this rare malignancy.

The oxygen evolution reaction (OER) is a vital half-reaction in many applications, such as the electrochemical H2O splitting, CO2, and N2 conversion processes. The OER involves a four-electron transfer and is a kinetically sluggish reaction that requires additional potential to drive. To enhance the electrochemical performance of the above-mentioned applications, highly efficient, corrosion-resistant, earth-abundant, and eco-friendly electrocatalysts are required. Here, we report a highly porous, minimally Ru-doped copper phosphate electrocatalyst obtained through co-precipitation. The optimized electrocatalyst (5% Ru-doped copper phosphate) exhibits a low overpotential of 340 mV to achieve 10 mA cm−2 compared to copper-based materials, and it remains stable over 20 h. The high performance is attributed to a high electrochemically effective surface area (ECSA) of 30.25 cm2, facilitating effective ion transportation at the electrode/electrolyte interface and excellent electrical conductivity. This result is supported by density functional theory calculations, which demonstrate that ruthenium enhances the electrochemical properties by increasing electronic conductivity, reducing the theoretical overpotential, and influencing the rate-determining step of the oxygen evolution reaction. Herein, the electrocatalyst is attractive for commercialization due to its utilization of minimal ruthenium in earth-abundant electrocatalysts, which offer competitive performance.

Hydrogen energy is a sustainable and clean source that can meet global energy demands without adverse environmental impacts. High-entropy oxides (HEOs), multielement (5 or more) oxides with an equiatomic or near-equatomic elemental composition, offer a novel approach to designing bifunctional electrocatalysts. This work explores (ZnNiCoFeY)xOy over MoS2 as a bifunctional electrocatalyst (HEO–MoS2) in an alkaline medium. The HEO was synthesized using a combustion process and loaded over MoS2 using an ultrasonic method. The synthesized HEO over MoS2 exhibits excellent performance, including long-term stability for over 24 h, an overpotential of 214 mV vs the reversible hydrogen electrode (RHE) for the hydrogen evolution reaction (HER), and 308 mV for the oxygen evolution reaction (OER) at 10 mA cm−2. This bifunctional electrocatalyst exhibits low overpotential for both the HER and the OER at high current densities. Additionally, HEO–MoS2 demonstrates smaller solution and charge transfer resistance values. The electrolyzer was assembled using bifunctional HEO–MoS2 electrodes for overall water splitting. These electrodes exhibited a low cell voltage of 1.65 V at 10 mA cm−2. The novel electrocatalyst was fabricated using a facile and scalable method that appeals to industrial applications.

The combination of heterocycles renders a new possibility to synthesize multicyclic compounds having improved biological activities. Furo[3,2-b]pyridine is a fused heterocyclic ring system comprising a furan ring attached at the third and second positions of pyridine. These heterocyclic compounds can be easily synthesized from versatile starting materials including pyridine, furan, benzofuran, and benzopyridine via cycloaddition, cycloisomerization, multicomponent, cross-coupling, and Dakin-type reactions by utilizing microwave, copper, and palladium based catalysts. Among the chemical transformations of furo[3,2-b]pyridine derivatives, the review covered acetylation, addition, condensation, chlorination, Suzuki coupling, Vilsmeier-Haack reaction, and nucleophilic substitution reactions. Furo[3,2-b]pyridine has attracted remarkable attention from researchers due to its wide range of pharmacological and biological applications as antibiotic, antiviral, antifungal, anticancer, inhibitors of nicotinic acetylcholine receptors, CLKs, e1F4A, DYRKIA, α-glucosidase and β-glucosidase. The purpose of the review is to discuss the chemistry of the title reported during 2019–2024.

Objectives Administrative databases such as voter registries contain a wealth of information about a large proportion of a population. This is especially true when longitudinal information about individuals is available, such as changes in their names, addresses, or self-reported ethnic attributes. Apparent changes in ethnic attributes might be due to perceptions of majority evaluations of ethnic groups. In this project, we analysed snapshots of a publicly available US voter database from 2015 to 2022, exploring if and how recent presidential elections impacted changes in voters' self-reported ethnic attributes. Approach Using bi-monthly snapshots of a publicly available US voter database from 2015 to 2022, we generated cohorts by linking active voters during seven twelve-month periods (2015/16 to 2021/22). These seven time periods included one mid-term and two presidential elections, and four control time spans before, between, and after these elections. We compared changes in self-reported ethnic attributes of voters during the times of elections versus the control time periods. Results Preliminary results reveal a substantial change to self-reported ethnic attributes during the periods leading to an election. A majority of such changes are by individuals from a specific ethnic group choosing not to report an ethnicity, an indication of their preference to not disclose ethnicity-related sensitive information. Conclusions We have shown how a publicly available voter database can be used to explore how self-reported ethnic attributes are modified by individual voters over time, and how the prevalence of such changes is influenced by political events such as presidential elections.

Objectives It has been shown that record linkage methods can induce bias in resulting datasets since the linkage quality may differ between ethno-racial groups. In this project, we used publicly available voter databases to investigate whether ethno-racial attributes can influence the similarities calculated using approximate string comparison functions on voters' names. Approach We used 11 annual snapshots of a publicly available US voter database between 2011 and 2021 with uniquely identifiable voter data. We extracted pairs of the same voter’s first and last name values from two consecutive snapshots where these values differ. We calculated string similarities and created similarity histograms for each of the available ethno-racial categories, and other sociodemographics variables such as gender and age. We characterized common patterns of name disagreements by ethno-racial groups and compared the shapes of these histograms using cumulative density distributions. Preliminary Results Across the 10 snapshot pairs, eligible voters with non-missing first and last names are included (N2011/2012 = 6,193,001, N2020/2021 = 7,852,763), describing 124,009 first name changes and 485,807 last name changes. Results will be presented as a series of density plots. Using Jaro-Winkler similarity scores of 0.7, 0.8 and 0.9 as threshold, we examined whether match rates differ by ethno-racial categories. Conclusions and Implications Using the same string similarity function on names of individuals of different ethno-racial groups may lead to different distributions of the resulting similarity values. Understanding the patterns of ethno-racial-based name changes in your particular dataset is crucial on selecting linkage parameters that would minimise ethno-racial bias.

Objectives Data linkage is the process of matching records that refer to the same entities (often people) across databases. In applications such as health research or government services, the databases to be linked are often sensitive and cannot be shared between organisations. Privacy-preserving record linkage (PPRL) aims to overcome this challenge by facilitating the comparison of encoded or encrypted records without having to share sensitive data. Most existing PPRL techniques are based on heuristics and they have limitations in the privacy protection they offer, such as being vulnerable to certain cryptanalysis attacks. Furthermore, existing PPRL methods have multiple parameters, which, if not set properly by the user, can result in sub-optimal linkage quality and reduced privacy protection. Approach We present a novel PPRL method that uses random reference q-gram sets to generate bit-arrays that represent sensitive values. Our method has a single parameter to be set by the user that trades scalability with linkage quality and privacy protection. All other parameters are either data-driven or have strong bounds based on this user parameter. Results We conceptually analyse our method and conduct experiments on multiple databases. The results demonstrate that our method provides high linkage quality and strong privacy protection while being scalable to link very large databases. Conclusion Our novel PPRL method provides high linkage quality, scalability, and improved privacy protection compared to existing PPRL methods such as Bloom filter encoding. A major advantage of our method is that it requires a single parameter to be set by the user.

IntroductionThe emergence and resurgence of pathogens have led to significant global health challenges. Wastewater surveillance has historically been used to track water-borne or fecal-orally transmitted pathogens, providing a sensitive means of monitoring pathogens within a community. This technique offers a comprehensive, real-time, and cost-effective approach to disease surveillance, especially for diseases that are difficult to monitor through individual clinical screenings.MethodsThis narrative review examines the current state of knowledge on wastewater surveillance, emphasizing important findings and techniques used to detect potential pathogens from wastewater. It includes a review of literature on the detection methods, the pathogens of concern, and the challenges faced in the surveillance process.ResultsWastewater surveillance has proven to be a powerful tool for early warning and timely intervention of infectious diseases. It can detect pathogens shed by asymptomatic and pre-symptomatic individuals, providing an accurate population-level view of disease transmission. The review highlights the applications of wastewater surveillance in tracking key pathogens of concern, such as gastrointestinal pathogens, respiratory pathogens, and viruses like SARS-CoV-2.DiscussionThe review discusses the benefits of wastewater surveillance in public health, particularly its role in enhancing existing systems for infectious disease surveillance. It also addresses the challenges faced, such as the need for improved detection methods and the management of antimicrobial resistance. The potential for wastewater surveillance to inform public health mitigation strategies and outbreak response protocols is emphasized.ConclusionWastewater surveillance is a valuable tool in the fight against infectious diseases. It offers a unique perspective on the spread and evolution of pathogens, aiding in the prevention and control of disease epidemics. This review underscores the importance of continued research and development in this field to overcome current challenges and maximize the potential of wastewater surveillance in public health.

Abstract Background Avian pathogenic E. coli (APEC) can cause localized or systemic infections, collectively known as avian colibacillosis, resulting in huge economic losses to poultry industry globally per year. In addition, increasing evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in regulating host inflammation in response to bacterial infection. However, the role of lncRNAs in the host response to APEC infection remains unclear. Results Here, we found 816 differentially expressed (DE) lncRNAs and 1,798 DE mRNAs in APEC infected chicken macrophages by RNAseq. The identified DE lncRNA-mRNAs were involved in Toll like receptor signaling pathway, VEGF signaling pathway, fatty acid metabolism, phosphatidylinositol signaling system, and other types of O-glycan biosynthesis. Furthermore, we found the novel lncRNA TCONS_00007391 as an important immune regulator in APEC infection was able to regulate the inflammatory response by directly targeting CD86. Conclusion These findings provided a better understanding of host response to APEC infection and also offered the potential drug targets for therapy development against APEC infection.

Background: Despite enormous attempts to stop the spread of tuberculosis (TB), TB continues to be a major global public health concern. A crucial group for influencing future public health understanding and policies is represented by students. Even though TB is a well-known disease, students’ misunderstandings and knowledge gaps might undermine successful TB control initiatives. This study aimed to identify student’s TB misconceptions and its impact on public health. A comprehensive literature review was conducted to explore researches focused on TB knowledge among students. Common themes from the chosen studies, such as knowledge of TB, its transmission, symptoms, risk factors and preventive methods were examined. We looked at how these information gaps can affect public health measures. The review revealed substantial gaps in students' knowledge of TB. Many students lacked a thorough understanding of TB symptoms, risk factors, and transmission. TB-related myths and stigma were also widely held. There is a need for educational initiatives, given the lack of understanding regarding TB prevention and potential therapies. The impression of tuberculosis (TB) as a past illness rather than a present-day hazard was also noticed, underscoring the demand for a revised public health message. The identified gaps regarding TB among students highlight the necessity of specialized educational efforts. Students can become champions for TB prevention and control by including TB-related issues in educational curriculum, workshops, and awareness campaigns. Wider spread of factual information can be facilitated by utilizing digital platforms and interactive teaching tools.

This article2 explores the sexuality of South African Muslim Indian wives in monogamous marriages, analyzing the effect of religious teachings and cultural norms on sexual experiences using hermeneutic phenomenology. The abrupt shift from religious norms that promote chastity to the expectation of sexual activity upon marriage, together with variations in desire and sexual preferences remain relatively underexplored within Muslim marriages. Under analysis is the dynamic between intimacy, desire, and shame. Drawing on empirical research, results highlight emotional and psychological challenges faced by Muslim women during marital sexual initiation due to their interpretations of religious teachings and limited sex education. Muslim wives experience that their sexual desire discrepancies negatively impact their mental health and self-esteem. There is the invocation of gendered sexual conceptions perpetuated by cultural conditioning which is also negotiated and subverted. Despite challenges, a transformative potential in marital relationships is indicated through agentival capacity, understanding, communication, and mutual sexual satisfaction.

The accurate speech recognition of the Holy Quran is crucial for maintaining the traditional recitation styles and pronunciations, which helps in preserving the authenticity of the Quranic teachings and ensuring their accurate transmission across generations. Though the application of freshly developed models to spoken and written Arabic and non-Arabic speech recognition has yielded highly accurate results, research on Holy Quran is still in its early levels. Indeed, speech recognition of the Holy Quran presents several challenges, including language complexity and the absence of a comprehensive dataset. This research aims to improve the accuracy of speech recognition models for the recital of the Holy Quran. A new dataset called comprehensive Quranic dataset version 1 (CQDV1) is created to serves the HQSR field. The dataset is publicly available for use by other researchers and includes recitations of the entire Quran (114 sura, recited by 35 reciters), based on Hafs from Asim narrative.The study explores the development of a speech recognition model for the accurate recital of the Holy Quran. The model combines a connectionist temporal classification (CTC)/attention loss function with a Bidirectional Long Short-Term Memory with projections (BLSTMP) architecture and a token-based recurrent neural network language model (RNNLM) using CQDV1 dataset. The results achieved were a token error rate (TER) of 6.4%, a word error rate (WER) of 10.4%, and a sentence error rate (SER) of 55.3% with $\lambda =0.2$ .

N-Arylpyrazoles are important building blocks in many biologically active compounds, natural products, pharmaceuticals, and industries. It is an important moiety of various drugs and exhibits extensive biological activities viz., antibiotic, anticancer, antifungal, anti-inflammatory, anti-coagulant, analgesic, antipyretic, anti-depressant, insecticidal, and hyperglycemic activities. Various protocols have been designed for the synthesis of N-arylpyrazoles facilitated by a wide variety of metal-based catalysts at high or room temperature, metal free reactions, various named reactions, multicomponent reactions, and those occurring under different electromagnetic radiations. Various ligands are found to promote Cu-catalyzed N-arylation of pyrazole under mild conditions in short time. This review describes the synthesis and biological applications of N-arylpyrazole derivatives reported during 2019–2023.

The purpose of this study was to synthesize the literature that has been established on the interrelationship of “knowledge spillovers and entrepreneurial ecosystem” through a systematic literature review. The query strings generated 85 articles, of which 51 were selected for final review. The analysis was performed using MySLR software that uses the Latent Dirichlet Allocation (LDA) method, and the effectiveness was measured through the perplexity score and coherence value of the topics. The results reveal that although a plethora of literature is available on these two topics individually, the mutual relationship between these two concepts is understudied. A stronger research interest was observed after 2018 which indicates the infancy of the topic as a whole, which is yet to be explored and empirically tested, specifically in developing economies. Most of the research was focused on the role of universities, innovation, geographic dynamics and policies with respect to entrepreneurial ecosystems. Results reveal the disparity of knowledge spillovers with regard to other contributors; significantly lesser attention was paid to its role in relation to the entrepreneurial ecosystem. Along with critical analysis and synthesis of literature, future directions have also been presented in the paper.

Abstract Background & Aims Non‐surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta‐analysis (NMA) was to evaluate and compare the effectiveness of ablative and non‐surgical therapies for patients with small HCC. Methods Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non‐surgical therapy versus any comparator in patients with HCC ≤3 cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. Results Thirty‐seven eligible RCTs were included (including over 3700 patients). Most were from China (n = 17) or Japan (n = 7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16–1.82), progression‐free survival (HR: 1.36, 95% CrI: 1.11–1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02–1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19–2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. Conclusions It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake.

Avian pathogenic E. coli (APEC), a widespread bacterium, results in serious economic losses to the poultry industry annually, and it poses a threat to human health due to the contaminated retail poultry meat and eggs. Recently, it has been demonstrated that long non-coding RNAs played important roles in regulating gene expression and the animal immune response. This study aimed to systematically explore the function of the novel long intergenic non-coding transcript, lincRNA-73240, upon APEC infection. A bioinformatics analysis indicated that lincRNA-73240 had no coding ability and a relative stable secondary structure with multiple hairpin rings. Moreover, the RT-qPCR results showed that lincRNA-73240 was highly expressed in lungs, heart, liver, spleen, cecum tonsils, thymus, ileum, bursa of Fabricius, harderian gland, and muscles in comparison to the cerebrum. Additionally, overexpression of lincRNA-73240 can promote the expression levels of inflammation, apoptosis, autophagy, and oxidative stress-related genes, as well as the production of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) upon APEC infection, which lead to cellular injury and apoptosis. These findings collectively establish a foundation for the study of the biological function of chicken lincRNA-73240 and provide a theoretical basis for further research on the molecular mechanisms of the chicken immune response.

In this article, we introduce a web-based malware detection system that leverages a deep-learning approach. Our primary objective is the development of a robust deep-learning model designed for classifying malware in executable files. In contrast to conventional malware detection systems, our approach relies on static detection techniques to unveil the true nature of files as either malicious or benign. Our method makes use of a one-dimensional convolutional neural network 1D-CNN due to the nature of the portable executable file. Significantly, static analysis aligns perfectly with our objectives, allowing us to uncover static features within the portable executable header. This choice holds particular significance given the potential risks associated with dynamic detection, often necessitating the setup of controlled environments, such as virtual machines, to mitigate dangers. Moreover, we seamlessly integrate this effective deep-learning method into a web-based system, rendering it accessible and user-friendly via a web interface. Empirical evidence showcases the efficiency of our proposed methods, as demonstrated in extensive comparisons with state-of-the-art models across three diverse datasets. Our results undeniably affirm the superiority of our approach, delivering a practical, dependable, and rapid mechanism for identifying malware within executable files.

Phytoremediation is a clean and green potentially cost-effective technology for remediating heavy metal-contaminated soil. In this study, a pot experiment was set up in which ornamental Tagetes erecta L. was grown in the pots with three concentrations i.e., 0, 5, and 10 % of contaminated soil amended with compost (2 %) in all pots of the experiment following three treatments of bacteria i.e., Co, Stutzerimonas stutzeri and Pseudomonas sundara. The experiment was composed of three replicates. After sixty days of the experiment, the plants were harvested. After harvesting morphological, physiological, antioxidants, and pollution parameters were investigated. By the inoculation of the S. stutzeri and P. sundara the height and biomass of the T. erecta enhanced as compared to control. Inoculated bacteria S. stutzeri and P. sundara enhanced the pigments, protein and water content of the plants. Bacteria also enhanced the antioxidants e.g., melatonin, catalase, peroxidase, ascorbate peroxidase and proline to minimize oxidative stress as evidenced by the reduction of hydrogen peroxide. The plants treated with S. stutzeri and P. sundara absorb high concentrations of heavy metals (chromium, cadmium and lead) in their parts. Post-analysis of the soil showed a decrease in pollution indicators. The results of this study can be used for the management and decontamination of the heavy metal polluted sites with the help of hyperaccumulator ornamental plants by inoculation of bacteria.

International policy agendas are increasingly focusing on the 21st century skills needed by future workers in response to Industry 4.0. In this study, we conduct a bibliometric analysis of 2662 articles published by 6579 authors in the last two decades to understand the structure of the scholarly knowledge in this field. We first identify influential articles, documents, journals and trends in this literature. We use co-citation analysis to identify foundational themes in the development of 21st century skills literature, then using bibliometric coupling, we identify communities in the current research front. We then use co-word analysis to identify future directions in the field. Overall, we find that research on 21st century skills has grown exponentially in the past two decades, however, few researchers focus primarily on this topic. The existing research is primarily dominated by psychologists, education researchers and technology researchers. We also find that specific disciplines such as industrial engineering and nursing are prominent contributors in the field, and that critical thinking and computational thinking are key areas of focus.

The phytoremediation technique is gaining excessive consideration as a promising method to remediate industrially contaminated soils with heavy metals. In this study, a pot experiment was performed in which the ornamental plant Helianthus annus L. was grown in the pots with three concentrations i.e., 0, 5, and 10 % of contaminated soil amended with compost (2 %) in all pots of the experiment following three treatments of bacteria i.e., Co, Stutzerimonas stutzeri and Pseudomonas sundara. After sixty days of the experiment, the plants were harvested and morphological, physiological, antioxidants and pollution parameters were investigated. The plant height and biomass of the sunflower were increased by the inoculation of S. stutzeri and P. sundara. Pigments e.g., chlorophyll a, b, carotenoids and proteins of the plants were enhanced. There was an increase in antioxidants e.g., catalase, peroxidase, ascorbate peroxidase and proline content and a decrease in hydrogen peroxide content of plants by inoculation of S. stutzeri and P. sundara. The bacteria boosted the uptake of heavy metals (cadmium, chromium and lead) in parts of plants. Post-harvested soil analysis indicated decreased electronic conductivity, total dissolved solids, bicarbonates and heavy metals in the soil. In the future, the combination of H. annus and bacteria could be a better technique to remediate the heavy metals in industrially polluted soils.

Objective: To assess the association of pre-eclampsia in women with raised CRP before 20 weeks of gestation. Study Design: Prospective cohort study, Place and Duration of Study: Department of Obstetrics and Gynaecology, Civil Hospital, Karachi Pakistan, from Jan to Aug 2019. Methodology: One hundred and sixty-eight women were included. 84 of 168 women had raised CRP, called as ExposedGroup, and 84 had normal CRP, called as Unexposed-Group. Blood samples were sent to assay serum CRP. Patients were thenfollowed up until the third trimester to observe whether women with elevated serum CRP >5 mg/l or women with normal levels of CRP developed pre-eclampsia. Results: The average age of the women was 26.30±5.15 years. The pre-eclampsia was significantly high in the Exposed-Group as compared to the Unexposed-Group (p=0.019). The pre-eclampsia was two times more likely in the Exposed-Group as compared to the Unexposed-Group (RR=1.73; 95% CI 1.07-2.79). Conclusion: Pre-eclampsia is more likely to occur before 20 weeks of pregnancy in women having raised CRP. Therefore, effective monitoring of CRP could help in timely management and prevent severity.

α-Terpineol is a monoterpenoid alcohol that has been widely used in the flavor, fragrance, and pharmaceutical industries because of its sensory and biological properties. However, few studies have focused on the microbial production of α-terpineol. The oleaginous yeast Rhodotorula toruloides is endowed with a natural mevalonate pathway and is a promising host in synthetic biology and biorefinery. The primary objective of this work was to engineer R. toruloides for the direct biosynthesis of α-terpineol. The improvement in monoterpenoid production was achieved through the implementation of modular engineering strategies, which included the enhancement of precursor supply, blocking of downstream pathways, and disruption of competing pathways. The results of these three methods showed varying degrees of favorable outcomes in enhancing α-terpineol production. The engineered strain 5L6HE5, with competitive pathway disruption and increased substrate supply, reached the highest product titer of 1.5 mg/L, indicating that reducing lipid accumulation is an efficient method in R. toruloides engineering for terpenoid synthesis. This study reveals the potential of R. toruloides as a host platform for the synthesis of α-terpineol as well as other monoterpenoid compounds.

Background and Objective: Isoproterenol (ISO) is a non-selective β-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of β-receptors by ISO can cause “cardiorenal syndrome,” a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury. Materials and Methods: The kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis. Results: ISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters. Conclusion: L-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.

Students need the ability to explore, think critically and analyze a problem for a logical and appropriate solution. Problem solving abilities accompanied with a belief in their abilities (self efficacy) will maximize student abilities in and get maximum grades. This research aims to analyze the correlation between self efficacy and students' problem-solving abilities in ecosystem material. The method used is a quantitative method with a correlational approach (relationship study). The data collection technique was in the form of a problem-solving ability test in the form of an essay about ecosystem and a self efficacy questionnaire. The data analysis technique uses the Product Moment correlation test. Based on the results of data analysis and hypothesis testing, a correlation coefficient value of 0.675 was obtained, which means that the correlation coefficient level is strong. It can be concluded that there is a correlation between self efficacy and problem-solving abilities of students in ecosystem material with a strong correlation coefficient.

This study investigates the influence of molybdenum (Mo) doping on the local atomic structure, morphology, and electrical properties of amorphous germanium telluride (GeTe) thin films. Structural and morphological studies show that Mo-doping inhibits the crystallization of amorphous GeTe thin films. Moreover, the crystallization temperature of the GeTe thin film increases from 197 to 317 °C with increasing Mo dopant concentration. The electrical properties of Mo-doped GeTe thin films are discussed in terms of the capacitance–voltage characteristics in temperatures range 27–357 °C. The optical bandgap values decrease from 0.67 to 0.55 eV when increasing Mo doping in GeTe thin film. Mo integration significantly impacts the Ge–Te bond lengths and structural symmetry, increasing the degree of disorder in amorphous GeTe thin films. This study demonstrates the effectiveness of Mo doping in enhancing the thermal stability of the amorphous phase of GeTe for its envisioned memory and brain-inspired computing applications.

Abstract Background With the increased interest in the inclusion of non-randomised data in network meta-analyses (NMAs) of randomised controlled trials (RCTs), analysts need to consider the implications of the differences in study designs as such data can be prone to increased bias due to the lack of randomisation and unmeasured confounding. This study aims to explore and extend a number of NMA models that account for the differences in the study designs, assessing their impact on the effect estimates and uncertainty. Methods Bayesian random-effects meta-analytic models, including naïve pooling and hierarchical models differentiating between the study designs, were extended to allow for the treatment class effect and accounting for bias, with further extensions allowing for bias terms to vary depending on the treatment class. Models were applied to an illustrative example in type 2 diabetes; using data from a systematic review of RCTs and non-randomised studies of two classes of glucose-lowering medications: sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Results Across all methods, the estimated mean differences in glycated haemoglobin after 24 and 52 weeks remained similar with the inclusion of observational data. The uncertainty around these estimates reduced when conducting naïve pooling, compared to NMA of RCT data alone, and remained similar when applying hierarchical model allowing for class effect. However, the uncertainty around these effect estimates increased when fitting hierarchical models allowing for the differences in study design. The impact on uncertainty varied between treatments when applying the bias adjustment models. Hierarchical models and bias adjustment models all provided a better fit in comparison to the naïve-pooling method. Conclusions Hierarchical and bias adjustment NMA models accounting for study design may be more appropriate when conducting a NMA of RCTs and observational studies. The degree of uncertainty around the effectiveness estimates varied depending on the method but use of hierarchical models accounting for the study design resulted in increased uncertainty. Inclusion of non-randomised data may, however, result in inferences that are more generalisable and the models accounting for the differences in the study design allow for more detailed and appropriate modelling of complex data, preventing overly optimistic conclusions.

Background A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function. Objective To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm). Design Systematic review and network meta-analysis. Data sources Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews. Review methods Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research. Results Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (n ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (n = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials. Limitations Many studies were small and of poor quality. No comparative studies were found for some therapies. Conclusions The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection. Study registration PROSPERO CRD42020221357. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information. Plain language summary Hepatocellular carcinoma is the most common type of primary liver cancer. There are a range of different treatments available for patients with early hepatocellular carcinoma. We looked for clinical trials in patients with small tumours (up to 3 cm) that compared different treatments. We brought together and analysed the results of these trials to see which treatments were most effective in terms of survival, progression, side effects and quality of life. Overall, the evidence has limitations; many trials had few patients and were of poor quality. Most were from China or Japan, where the common causes of liver disease and treatments available differ from those in the United Kingdom. The results of our analyses were very uncertain so we cannot be sure which treatment is the best overall. We did find that three treatments – radiofrequency ablation, microwave ablation and surgery – were generally more effective than percutaneous ethanol injection and percutaneous acid injection. There was not enough evidence to be certain which treatment was better when radiofrequency ablation was compared with laser ablation, microwave ablation, proton beam therapy or surgery. We found only poor-quality, non-randomised trials on high-intensity focused ultrasound, cryoablation and irreversible electroporation. There was very little evidence on treatments that combined radiofrequency ablation with other therapies. We found no studies that compared electrochemotherapy, histotripsy, stereotactic ablative radiotherapy or wider radiotherapy techniques with other treatments. Only two studies reported data on quality of life or patient satisfaction. We discussed the findings with patients and clinical experts. Stereotactic ablative radiotherapy was highlighted as a treatment that requires further research; however, it is only appropriate for certain subgroups of patients. Feasibility studies could inform future clinical trials by exploring issues such as whether patients are willing to take part in a trial or find the treatments acceptable. Scientific summary Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Around one-third of people with cirrhosis go on to develop HCC. The prognosis of symptomatic HCC is poor, so the National Institute for Health and Care Excellence recommends that patients with cirrhosis are monitored for early HCC with six-monthly ultrasound scans. Patients with early HCC and good liver function can be offered surgical or non-surgical interventions with curative intent. However, liver resection is not always possible due to the location of the tumour, poor liver function or portal hypertension, and liver transplantation is limited by availability. Therefore, ablative or non-surgical therapies are frequently used for treating early HCC, including microwave ablation (MWA) and radiofrequency ablation (RFA). There has been no definitive assessment of these therapies. Objectives The aim of this project was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. The key objectives were to: systematically identify all randomised controlled trials (RCTs) of ablative and non-surgical therapies for HCC evaluate their quality and applicability to UK populations determine the comparative effectiveness of therapies using network meta-analysis (NMA) where the evidence base is insufficient, supplement the RCT evidence with high-quality, non-randomised, prospective comparative studies identify priority areas where additional high-quality evidence is required (in collaboration with patients and clinicians) assess whether future economic analysis would be feasible and worthwhile. Methods Systematic review of randomised controlled trials Nine databases (including MEDLINE, Embase, CENTRAL, Science Citation Index) were searched for RCTs and systematic reviews published from 2000 to March 2021. Two trial registries were searched in April 2021 to identify ongoing and unpublished RCTs. The reference lists of relevant systematic reviews were checked and clinical advisors were consulted. Randomised controlled trials of patients with HCC up to 3 cm in size (or data on a subgroup(s) of patients with tumours ≤ 3 cm) were eligible for inclusion. Any ablative or non-surgical therapy was eligible, including: RFA MWA laser ablation high-intensity focused ultrasound (HIFU) cryoablation percutaneous ethanol injection (PEI) percutaneous acetic acid injection (PAI) irreversible electroporation (IRE) transarterial chemoembolisation (TACE) transarterial embolisation selective internal radiation therapy electrochemotherapy (ECT) histotripsy stereotactic ablative radiotherapy [SABR; the term stereotactic body radiotherapy (SBRT) is also used for this technology] wider radiotherapy techniques. Any comparator was eligible, except a different method of undertaking the same intervention. Outcomes of interest were overall survival (OS), progression-free survival (PFS), time to progression (TTP), serious adverse events (AEs), intervention-specific AEs and quality of life. Titles and abstracts were screened by one reviewer, with 10% checked by another reviewer. Full texts were screened by two reviewers independently. Data extraction was checked by a second reviewer. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. When studies did not report hazard ratios (HRs) and their variances, Kaplan–Meier data were extracted. Network meta-analysis After mapping the identified RCTs, NMAs were conducted for four outcomes: OS, PFS, overall recurrence and local recurrence. They were conducted in a Bayesian framework using Markov chain Monte Carlo techniques. The NMAs were used to assess and rank interventions by comparative effectiveness. Threshold analysis Threshold analysis was conducted at the contrast level to examine the impact of potential changes to the evidence on each treatment contrast. Results of the analysis were used to identify treatment comparisons which lacked robust RCT evidence and where non-randomised evidence should be sought for further review. Systematic review of non-randomised evidence A second systematic review of non-randomised evidence was undertaken. This review included studies of comparisons where additional evidence could plausibly change the NMA conclusions, as identified by the threshold analysis. Four databases were searched in August 2021 for studies that compared the selected interventions (RFA, MWA and laser ablation), either with each other or with resection. The databases were also searched in July 2021 for interventions that the advisory group identified as being of particular interest and where there was no RCT evidence: HIFU, cryoablation, IRE, ECT, histotripsy, SABR and wider radiotherapy techniques. Prospective non-randomised comparative trials of patients with HCC up to 3 cm (or data on a subgroup(s) of such patients) were eligible. The outcomes of interest were OS, PFS, TTP and quality of life. Methods of screening and data extraction were the same as outlined above. A validity assessment tool for non-randomised trials was developed. Updated network meta-analysis and threshold analysis Where the non-randomised trials were of sufficient quality, the NMAs were repeated after pooling (without any adjustments) the non-randomised evidence with the RCT evidence, to assess whether estimates were improved. A threshold analysis was conducted on the updated NMA results to explore robustness and sensitivity to bias of the new results. Results Systematic review of randomised controlled trial results Thirty-seven RCTs were included. Most were small, with sample sizes ranging from 30 to 308 patients. The majority of RCTs were conducted in China or Japan. The most frequently assessed therapy was RFA. The majority of RCTs assessed OS, PFS/disease-free survival and/or recurrence, along with response and AEs. One RCT assessed patient satisfaction. The RoB judgement was low for 9 RCTs, high for 12 RCTs and some concerns for 14 RCTs (two RCTs that reported no relevant outcomes were not assessed). For many comparisons, data were limited. Based on a narrative synthesis, RFA appears to be better than both PEI and PAI in terms of OS, PFS and recurrence, although AEs were more frequent after RFA. PAI appears to have similar effectiveness to PEI. For RFA versus resection, results were inconsistent, with some RCTs favouring RFA and some resection; AEs were more frequent after resection. Data from RCTs comparing RFA with MWA, laser ablation or proton beam therapy were limited. RCTs assessing RFA in combination with other treatments were also limited by small sample sizes. AEs were reported inconsistently. There was no RCT evidence for HIFU, cryoablation, IRE, ECT, histotripsy, SABR or wider radiotherapy techniques. Network meta-analysis and threshold analysis results The treatment rankings from the NMAs were very uncertain for all four outcomes (OS, PFS, overall and local recurrence). There was no meaningful difference in effectiveness for many of the treatment comparisons. There was evidence that PEI is worse than RFA for OS [HR 1.45, 95% credible interval (CrI) 1.16 to 1.82], PFS (HR 1.36, 95% CrI 1.11 to 1.67), overall recurrence [relative risk (RR) 1.19, 95% CrI 1.02 to 1.39] and local recurrence (RR 1.80, 95% CrI 1.19 to 2.71). PAI was worse than RFA for PFS (HR 1.63, 95% CrI 1.05 to 2.51). Resection was better than PEI for OS (HR 0.60, 95% CrI 0.39 to 0.92). RFA combined with PEI decreased the risk of local recurrence compared with PEI alone (RR 0.33, 95% CrI 0.12 to 0.94). Radiofrequency ablation + iodine-125 appears superior to RFA alone in terms of OS (HR 0.50, 95% CrI 0.31 to 0.80) and overall recurrence (RR 0.69, 95% CrI 0.48 to 0.99). There was also evidence to suggest that RFA + iodine-125 is better than PEI, PAI, TACE + PAI, RFA + TACE and laser ablation for OS, and better than PEI and TACE + PEI for overall recurrence. However, according to our clinical advisors RFA + iodine-125 is only used in selected centres in China. There was evidence to suggest an increased risk of overall recurrence with MWA + sorafenib, compared with both resection (RR 2.09, 95% CrI 1.12 to 3.89) and RFA + iodine-125 (RR 2.93, 95% CrI 1.31 to 6.56). Also, RFA + systemic chemotherapy decreased the risk of overall recurrence compared with MWA + sorafenib (RR 0.26, 95% CrI 0.08 to 0.92). The threshold analysis suggested that additional evidence could plausibly change the NMA result for comparisons including RFA, MWA, laser ablation, RFA + TACE, RFA + systemic chemotherapy or RFA + iodine-125. RFA, MWA and laser ablation were agreed to be interventions of interest by the advisory group. Systematic review of non-randomised evidence results Fourteen non-randomised studies were identified. The majority were conducted in China or Japan, with sample sizes ranging from 21 to 740 patients. No comparative studies were identified on ECT, histotripsy, SABR or wider radiotherapy techniques. The quality and reporting of the non-randomised studies were poor; 12 had a high RoB. Several studies allocated patients to treatments based on tumour characteristics, so there were potentially prognostic differences between groups at baseline. There was one study with a low RoB. It compared RFA with MWA and included 42 patients. Local tumour progression was similar between groups but new intrahepatic tumours were more frequent in the RFA group. One study of RFA compared with resection had an unclear RoB and included 346 patients. It reported significantly better health-related quality of life (HRQoL), fewer AEs and a shorter hospital stay in the RFA group. Updated network meta-analyses and threshold analysis results Due to the significant limitations of the non-randomised studies identified, only the two studies that were not at a high RoB were included in the updated NMAs. Additional non-randomised comparative data (RFA vs. MWA vs. IRE) made available prior to publication by a clinical advisor were also included. Updated NMAs using RCT and non-RCT evidence were undertaken for OS, PFS and local recurrence. Most results of the updated NMAs were consistent with the original results. There remained a high level of uncertainty in treatment rankings. However, the updated NMAs suggested that MWA improves OS and PFS compared with PEI (OS: HR 0.60, 95% CrI 0.40 to 0.90; PFS: HR 0.66, 95% CrI 0.46 to 0.95) and PAI (OS: HR 0.48, 95% CrI 0.24 to 0.99; PFS: HR 0.55, 95% CrI 0.33 to 0.94). Resection also improves PFS compared with PEI (HR 0.72, 95% CrI 0.54 to 0.96) and PAI (HR 0.61, 95% CrI 0.38 to 0.98). The NMA showed IRE to be worse than RFA (RR 2.97, 95% CrI 1.45 to 6.09) and RFA + PEI (RR 4.96, 95% CrI 1.50 to 16.36) for local recurrence, although the CrIs were very wide for both comparisons. There was also evidence that RFA + iodine-125 is better than resection in terms of OS (HR 0.53, 95% CrI 0.30 to 0.94). The threshold analysis suggested that additional evidence could plausibly change the NMA result for comparisons including MWA, RFA, IRE, RFA + TACE and laser. Feasibility of economic modelling Limitations in available clinical data may impact the feasibility of undertaking robust economic analysis. However, a value of information (VOI) analysis may be helpful as there are currently several treatments with limited evidence on effectiveness. VOI analysis quantifies the value of reducing decision uncertainty in monetary terms. This can then be compared with the costs of conducting further studies. This could help prioritise which treatments should (or should not) be assessed in future trials. This may be of particular relevance in considering treatments that are currently rarely used in NHS practice but may be effective. Patient and public involvement The project team included a patient collaborator, who was involved throughout the project. Four additional patients were recruited to the project advisory group, attending meetings at key stages of the project. Patients provided helpful information about the outcomes most important to them, which informed the development of the data extraction tool. Patients were surprised by the lack of data on patient preference and quality-of-life outcomes. Patient and public involvement added context to the review findings and informed the conclusions of the report and recommendations for further research. Workshop Two workshops were held with clinicians and patients to discuss the project findings and identify key priorities for future research. It was agreed that MWA would be the most appropriate comparator in future trials as it is widely used as the standard of care in the UK, and therapies that are more complex to deliver were considered unlikely to replace it. MWA is preferred over RFA due to technological advances and ease of use, rather than data on improved clinical effectiveness. However, future research may be most useful if focused on the subgroup of patients with tumours in challenging locations, less fit patients and those with incomplete response to primary therapy. SABR and proton beam therapy were considered to be of particular interest. They are not suitable for patients with advanced or moderately advanced liver disease and, unlike ablation, can usually only be delivered once, but may be appropriate for a subgroup of patients. Histotripsy is at an early stage of regulatory approval, so should not be assessed until efficacy has been demonstrated. It may be most feasible to undertake an international multicentre RCT as the marginal benefit of novel treatments compared with the existing standard of care is likely to be small, so future studies would need to be large to demonstrate a significant difference in outcomes, and the number of early HCC patients in the UK eligible for all treatments is limited. Outcomes that should be assessed in future trials include local recurrence, overall recurrence, OS, PFS, HRQoL and patient acceptability. Conclusions Implications for health care There are considerable limitations to the evidence on ablative and non-surgical therapies for early and very early HCC. There is insufficient evidence to draw any conclusions on quality-of-life outcomes. The only firm conclusions that can be drawn from the available data are that PEI and PAI are inferior to RFA, and also appear to be inferior to MWA and resection for certain survival outcomes. MWA and resection are the first-line standard of care for single HCC ≤ 3 cm in the UK. The uptake of specific ablative therapies in the UK appears to be based more on technological advancements and ease or speed of use than on high-quality evidence demonstrating superior clinical effectiveness. Recommendations for research It is difficult to make firm recommendations for research based on our findings. There are currently no comparative data on several ablative and non-surgical therapies, particularly those treatments reserved for the subgroup of patients with more challenging tumours. However, owing to the small number of such patients who would be eligible for both treatment arms within a trial, along with the marginal benefit of novel treatments compared with the existing standard of care, it is likely to be difficult to recruit sufficient numbers of patients. Future studies should assess local recurrence, overall recurrence, OS, PFS, HRQoL and patient acceptability, using clear and consistent definitions, in order to allow results to be compared across studies. Further research on SABR, and possibly other technologies, such as IRE, is required to identify where they should sit in the treatment pathway. Feasibility studies could address potential issues and complexities in undertaking research in this area prior to undertaking a trial. This would enable: investigation of the acceptability of the intervention (and comparator) to both clinicians and patients, and their willingness to participate in a trial; the practicality of delivering the intervention; and the ability to measure relevant outcomes. Study registration This study is registered as PROSPERO CRD42020221357. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.

Objectives ‘Healthier Wealthier Families’ (HWF) seeks to reduce financial hardship in the early years by embedding a referral pathway between Australia’s universal child and family health (CFH) services and financial counselling. This pilot study investigated the feasibility and short-term impacts of HWF, adapted from a successful Scottish initiative.Methods Setting: CFH services in five sites across two states, coinciding with the COVID-19 pandemic. Participants: Caregivers of children aged 0–5 years experiencing financial hardship (study-designed screen). Design: Mixed methods. With limited progress using a randomised trial (RCT) design in sites 1–3 (March 2020–November 2021), qualitative interviews with service providers identified implementation barriers including stigma, lack of knowledge of financial counselling, low financial literacy, research burden and pandemic disruption. This informed a simplified RCT protocol (site 4) and direct referral model (no randomisation, pre–post evaluation, site 5) (June 2021–May 2022). Intervention: financial counselling; comparator: usual care (sites 1–4). Feasibility measures: proportions of caregivers screened, enrolled, followed up and who accessed financial counselling. Impact measures: finances (quantitative) and other (qualitative) to 6 months post-enrolment.Results 355/434 caregivers completed the screen (60%–100% across sites). In RCT sites (1–4), 79/365 (19%–41%) reported hardship but less than one-quarter enrolled. In site 5, n=66/69 (96%) caregivers reported hardship and 44/66 (67%) engaged with financial counselling; common issues were utility debts (73%), and obtaining entitlements (43%) or material aid/emergency relief (27%). Per family, financial counselling increased income from government entitlements by an average $A6504 annually plus $A784 from concessions, grants, brokerage and debt waivers. Caregivers described benefits (qualitative) including reduced stress, practical help, increased knowledge and empowerment.Conclusions Financial hardship screening via CFH was acceptable to caregivers, direct referral was feasible, but individual randomisation was infeasible. Larger-scale implementation will require careful, staged adaptations where CFH populations and the intervention are well matched and low burden evaluation.Trial registration number ACTRN12620000154909.

Madam, The proton-pump inhibitors (PPIs) belong to a class of medications that reduce stomach acid production by irreversibly inhibiting the stomach's H+/K+ ATPase pump. These medications are used in the treatment of many conditions, such aspeptic ulcer, gastroesophageal reflux, as part of H. Pylori eradication, gastrinomas, Barrett’s oesophagus and many other conditions. They are considered to be the most potent inhibitors of acid secretion, and have largely supplanted the H2 receptor antagonists and antacids. They are also among the most widely sold medications worldwide. The class of proton pump inhibitors is listed on WHO’s list of essential medicines.1Proton pump inhibitors are generally well tolerated. However, headache, nausea, diarrhoea, abdominal pain, fatigue, and dizziness are identified as some of the common side effects. Due to their efficacies and low risk profile, PPIs are often prescribed for extend than required period. Several recent studies have shown that long-term PPI use is associated with various adverse outcomes. A 2023 study published in JAMA Network Open demonstrated that long-term use of PPIs may lead to an increased risk of acquiring extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing enterobacterales.2Another study3 published in 2022 showed that PPI use was the only modifiable factor associated with the carriage of ESBL producers in residents of long-term care facilities. These studies add to the expanding list of adverse outcomes associated with PPIs. Other adverse events of long-term PPI use, include the risk of fractures, pneumonia, Clostridium difficile diarrhoea, hypomagnesaemia, vitamin B12deficiency, chronic kidney disease, and dementia.4 Proton pump inhibitors are still used widely in Pakistan. These new findings are concerning as ESBL-producing Enterobacteriaceae are highly prevalent in Pakistan. A meta-analysis showed that the overall pooled proportion of ESBLs in Pakistan is 40%5 whereas the German population showed an estimated ESBL proportion in the range of 10 to 15% and a US census reported 4 to 12% resistance due to ESBLs.5 This calls for a strict prescription control of PPIs by Pakistani physicians, and the duration of PPI use should not extend for longer than needed. In addition, the practice of PPI’s over the counter sale by the pharmacists in Pakistan should be stopped. Additional precautions should be taken in hospitalized patients who are using PPIs to prevent them from getting multi-drug resistant infections.

The purpose of this paper is to investigate the impact of managerial (Chief Executive Officer) overconfidence on corporate financing decision with the mediating role of risk perception. This study indicates that psychological biases affect the risk perception and ultimately financing decision of top management of an organization. The research design is causal and primary data has been used to test the proposed relationship. Among all the companies listed in the Pakistan Stock Exchange, researchers have selected top executives of 200 companies as a sample. E-Questionnaire has been used to collect the required data through LinkedIn and other mailing sources. Researcher has done a linear regression to find the relationship between independent variable overconfidence and dependent variable that is leverage. Baron and Kennys four-step mediation has been used to test the mediation effect of risk perception. Results of this study conclude that there is a significant positive relationship between overconfidence of CEO and leverage while there is a significant negative relationship between CEO overconfidence and risk perception. However, there is an insignificant result for the mediating role of risk perception between CEO overconfidence and leverage. Extensive research work is available on basic topic of how dividend policy and capital structure affect corporate performance; however, we found insufficient literature on psychological forces (behavioural biases) for financial decision making. The gap is covered by this study through explaining the impact of behavioural biases on corporate financial decisions which further distresses corporate performance. The results are significant for company top management, regulators and policy makers. This study as an empirical evidence is also helpful for researchers, academicians, and practitioners to understand and implement the notions coined by behavioural finance, regarding the effects of behavioural biases on corporate financial decisions that ultimately affects the corporate performance. The results are in line with previous studies on emerging economies.

This study aims to investigate the impact of banking-sector concentration on the banks’ liquidity creation in GCC countries over the period from 2012 to 2018 by using a dynamic GMM panel procedure. The results suggest that increased bank competition reduces banks’ liquidity creation across the GCC countries. The study’s findings are in line with the ‘financial fragility hypothesis” according to which banks to reduce their lending activities when competition is high in the market. The evidence suggests that the banking industry is different from others, and pro-competitive policies in the banking industry can reduce liquidity provision by banks. In the context of policy implications, a concentrated banking system discourages capital provision to firms; hence, regulators have to take appropriate measures to resolve the problem of a reduced supply of capital. Government must regulate the banking sector by keeping in view their long-run goal as competition is a double-edged sword in banking.

The purpose of this research study was to investigate and determine the impact of teacher’s attitudes and beliefs on their behavioral intentions to integrate ICT into their science lessons and to establish the impact of a professional development program underpinned by the principles of empowerment evaluation (EE) on their attitudes and beliefs. The participants were selected from five high schools in Johannesburg, South Africa. A validated questionnaire was used to identify teachers’ attitudes and beliefs and to measure the impact of their attitudes and beliefs on their behavioral intentions to integrate ICTs into their science lessons. The findings from this research study indicated that the empowerment evaluation approach positively impacted the teacher’s attitudes and beliefs as well as improved their behavioral intentions to integrate ICT into their science lessons. Furthermore, this study revealed that the more confident and competent a teacher felt to integrate ICT into his/her lessons, the more likely he/she would be to integrate ICT into their lessons. Therefore, teachers’ behavioral intentions are important in predicting whether they will integrate ICT into their lessons.

The rise of multidrug resistant microbial species is a major public health problem worldwide. Complementary natural sources with antimicrobial potentials including plants and plant-based products such as honey, are currently receiving great attention. As such, this study aimed to evaluate the medicinal potentials of honey by testing its antibacterial efficacy against Pseudomonas aeruginosa isolates associated with wounds infection. Clinical isolates of Pseudomonas aeruginosa from infected wounds such as sepsis, bite, surgical, laceration and gunshots were obtained from Federal Teaching Hospital Katsina. The antibacterial activity of honey was assayed by Agar well diffusion technique using different concentrations of honey; 25%, 50%, 75%, and 100% (v/v). Minimum Inhibitory Concentration and Minimum Bactericidal Concentration of honey were also determined. The mean zone of inhibition of honey against the isolates range from 10.6 mm to 22.6 mm. Moreover, the inhibitory effects of honey at 100% (v/v) differ significantly compared to other concentrations. The Minimum Inhibitory Concentration of honey was determined to be 25% (v/v) while the Minimum Bactericidal Concentration was estimated to be 75% (v/v). Pseudomonas aeruginosa isolate from gunshot wound was more susceptible to honey and ciprofloxacin (control) compared to Pseudomonas aeruginosa from other wound types. This study's findings demonstrated honey's efficacy in treating wound infections. Natural products, such as honey, have enormous potential for combating antibiotic resistance. In vivo studies should be carried out to further study the impact of honey on biological systems.

IntroductionVaccine hesitancy is a global health threat undermining control of many vaccine-preventable diseases. Patient-level education has largely been ineffective in reducing vaccine concerns and increasing vaccine uptake. We built and evaluated a personalized vaccine risk communication website called LetsTalkShots in English, Spanish and French (Canadian) for vaccines across the lifespan. LetsTalkShots tailors lived experiences, credible sources and informational animations to disseminate the right message from the right messenger to the right person, applying a broad range of behavioral theories.MethodsWe used mixed-methods research to test our animation and some aspects of credible sources and personal narratives. We conducted 67 discussion groups (n = 325 persons), stratified by race/ethnicity (African American, Hispanic, and White people) and population (e.g., parents, pregnant women, adolescents, younger adults, and older adults). Using a large Ipsos survey among English-speaking respondents (n = 2,272), we tested animations aligned with vaccine concerns and specific to population (e.g., parents of children, parents of adolescents, younger adults, older adults).ResultsDiscussion groups provided robust feedback specific to each animation as well as areas for improvements across animations. Most respondents indicated that the information presented was interesting (85.5%), clear (96.0%), helpful (87.0%), and trustworthy (82.2%).DiscussionTailored vaccine risk communication can assist decision makers as they consider vaccination for themselves, their families, and their communities. LetsTalkShots presents a model for personalized communication in other areas of medicine and public health.

Objective: To find out the frequency of hypoglycemia in Type-2 Diabetics having nephropathy Methodology: This cross-sectional observational study was carried out in Medical Teaching Institute Khyber Teaching Hospital. Department of Medicine, from August 21, 2020, to January 21, 2021. Two-hundred and eighty-one (281) patients with Type 2 diabetic nephropathy were observed in due course and were subjected to detailed history and examination. A sample of 5 ml venous blood was obtained from the patients to measure blood glucose levels to detect hypoglycemia. Experienced pathologists analyzed all investigations. Results: The mean ± Standard deviation (SD) of age in this study was 60± 10.26 years. Female patients outnumbered males in this study. Hypoglycemia was reported in 21% of patients while 79% did not have hypoglycemia. Conclusion: Type-2 diabetics having nephropathy are prone to hypoglycemia. These patients should be carefully observed for clinical and biochemical features of hypoglycemia .

Temperature-dependent capacitance–voltage and conductance–voltage measurements of 200-nm-thick germanium telluride (GeTe) thin films deposited via direct current magnetron sputtering were investigated. Measurements were performed across a temperature range of 27–357 °C, with a sweep of voltage values from −20 to +20 V at an operating frequency of 1 MHz. An amorphous–crystalline transition temperature (Tc) of 197 °C was found. Below Tc, the GeTe films were highly resistive, and their capacitance was insensitive to the applied bias voltage and temperature. Above Tc, the capacitance showed strong dependence on temperature, owing to the triggering of GeTe crystallization incorporating nucleation and growth processes. Applied bias voltage did not show a profound impact on the GeTe capacitance even after crystallization, but it had an observable impact on the film conductance beyond 250 °C. Moreover, the GeTe thin film capacitance increased by a factor of 13 upon crystallization. Hall-effect measurements revealed that the film conductivity increased upon crystallization, as did the hole concentration and mobility. Cross-sectional transmission electron microscopy demonstrated that the GeTe thin films crystallize via a nucleation-dominated crystallization mechanism.

The adoption of fully battery-powered electric vehicles (EVs) in Kuwait is currently at less than one percent of the population, and hence Kuwait has the lowest index rank among countries around the globe. Effectively, only Kuwaiti nationals have the opportunity to own EVs, as there are no fast direct-current charging stations in Kuwait, and Kuwaiti landlords (expats cannot own real estate) do not allow the installation of EV-charging home wall boxes at their rented properties. Given these facts, this paper only focuses on the preferences of Kuwaiti nationals, even though they only constitute 25 percent of the population of Kuwait. To accomplish the present objectives, a quantitative descriptive method (closed-ended questions) was used to collect data from a sample of 227 Kuwaiti nationals who were representative of the owners of half a million internal combustion engine (ICE) cars and that were categorized as early majority consumers. The findings of the present study indicate that over 50 percent of the respondents would prefer to buy an EV in the following three years when certain criteria were satisfied, including government-controlled pricing policies and recharging point availability, high-speed roads, and free EV-dedicated parking spaces. Furthermore, over 40 percent of respondents stated that they would contemplate purchasing an electric vehicle if the price of gasoline or diesel increased by 19 to 50 percent. The findings also indicated that more than 40 percent of respondents believed that EVs are fire- and crash-safe, and roughly 50 percent of the respondents would be willing to pay between 6 and 20% more for an EV because they believe that EVs are ecofriendlier vehicles and are significantly faster than conventional petrol vehicles. Additionally, respondents rewarded those vehicles with an excellent mark because of their ecological, economical, and technological attributes and benefits.

Emerging brain technologies have significantly transformed human life in recent decades. For instance, the closed-loop brain-computer interface (BCI) is an advanced software-hardware system that interprets electrical signals from neurons, allowing communication with and control of the environment. The system then transmits these signals as controlled commands and provides feedback to the brain to execute specific tasks. This paper analyzes and presents the latest research on closed-loop BCI that utilizes electric/magnetic stimulation, optogenetic, and sonogenetic techniques. These techniques have demonstrated great potential in improving the quality of life for patients suffering from neurodegenerative or psychiatric diseases. We provide a comprehensive and systematic review of research on the modalities of closed-loop BCI in recent decades. To achieve this, the authors used a set of defined criteria to shortlist studies from well-known research databases into categories of brain stimulation techniques. These categories include deep brain stimulation, transcranial magnetic stimulation, transcranial direct-current stimulation, transcranial alternating-current stimulation, and optogenetics. These techniques have been useful in treating a wide range of disorders, such as Alzheimer's and Parkinson's disease, dementia, and depression. In total, 76 studies were shortlisted and analyzed to illustrate how closed-loop BCI can considerably improve, enhance, and restore specific brain functions. The analysis revealed that literature in the area has not adequately covered closed-loop BCI in the context of cognitive neural prosthetics and implanted neural devices. However, the authors demonstrate that the applications of closed-loop BCI are highly beneficial, and the technology is continually evolving to improve the lives of individuals with various ailments, including those with sensory-motor issues or cognitive deficiencies. By utilizing emerging techniques of stimulation, closed-loop BCI can safely improve patients' cognitive and affective skills, resulting in better healthcare outcomes.

Kearns-Sayre syndrome (KSS) is one of the three classic and overlapping phenotypes that result from simplex mitochondrial DNA (mtDNA) deletion syndromes. The rarity of the syndrome has led to a paucity of reported cases in the literature. We present the case of a young female who presented with drooping of her right eyelid, generalized muscle wasting, fatigability of the proximal muscles of her limbs, a nasal twang in her voice, bilateral progressive ophthalmoplegia, and a history of surgically correct ptosis of her left eyelid. Fundoscopy revealed salt-and-pepper-like retinopathy bilaterally. Her electrocardiogram (ECG) findings included an inferior infarct and a left anterior fascicular block. This case highlights the importance of multifaceted investigations and prompt diagnosis in resource-limited settings for effective management in suspected cases of KSS.

Human serum albumin (HSA) is a multi-domain macromolecule with diverse ligand binding capability because of its ability to allow allosteric modulation despite being a monomeric protein. Physiologically, HSA act as the primary carrier for various exogenous and endogenous compounds and fatty acids, and alter the pharmacokinetic properties of several drugs. It has antioxidant properties and is utilized therapeutically to improve the drug delivery of pharmacological agents for the treatment of several disorders. The flexibility of albumin in holding various types of drugs coupled with a variety of modifications makes this protein a versatile drug carrier with incalculable potential in therapeutics. This review provides a brief outline of the different structural properties of HSA, and its various binding sites, moreover, an overview of the genetic, biomedical, and allosteric modulation of drugs and drug delivery aspects of HSA is also included, which may be helpful in guiding advanced clinical applications and further research on the therapeutic potential of this extraordinary protein.

The influence of COVID-19 on individuals, businesses, and corporations is indisputable. Many markets, particularly financial markets, have been severely shaken and have suffered significant losses. Significant issues have arisen in supply chain networks, particularly in terms of financing. The COVID-19 consequences had a significant effect on supply chain financing (SCF), which is responsible for finance supply chain components and improved supply chain performance. The primary source of supply chain financing is financial providers. Among financial providers, the banking sector is referred to as the primary source of financing. Any hiccup in the banking operational systems can have a massive influence on the financing process. In this study, we attempted to comprehend the key consequences of the COVID-19 epidemic and how to mitigate COVID-19’s impact on Pakistan’s banking industry. For this, three extended hybrid approaches which consists of TOPSIS, VIKOR, and Grey are established to address the uncertainty in supply chain finance under q-rung orthopair probabilistic hesitant fuzzy environment with unknown weight information of decision-making experts as well as the criteria. The study is split into three parts. First, the novel q-rung orthopair probabilistic hesitant fuzzy (qROPHF) entropy measure is established using generalized distance measure under qROPHF information to determine the unknown weights information of the attributes. The second part consists of three decision-making techniques (TOPSIS, VIKOR, and GRA) in the form of algorithm to tackle the uncertain information under qROPHF settings. Last part consists of a real-life case study of supply chain finance in Pakistan to analyze the effects of emergency situation of COVID-19 on Pakistani banks. Therefore, to help the government, we chose the best alternative form list of consider five alternatives (investment, government support, propositions and brands, channels, and digital and markets segments) by using proposed algorithm that minimize the effect of COVID-19 on supply chain finance of Pakistani banks. The results indicate that the proposed techniques are applicable and effective to cope with ambiguous data in decision-making challenges.

Given the growing influence of non-academic organizations in the policy sphere, it is important to investigate the evidence both produced by and relied on by these organizations. Using citation analysis, a methodology primarily used in academic literature, we investigated the evidence base supporting the grey literature published by leading global management consulting firms (GMCFs) and international organizations (IOs). With the topic of the skills needed for the future of work as a case study, we collected 234 reports published by influential GMCFs and IOs over twenty years. By extracting references from the bibliographies of these reports we: 1) analyzed referencing patterns by measuring citation counts, institutional self-referencing and utilization of scholarly sources; 2) compared reference patterns across GMCFs and IOs; and 3) described the most influential sources. Overall, both GMCFs and IOs showed increasing reliance on grey literature, demonstrated high levels of self-referencing, and had considerable variation in the number of sources referred to. Across type of publishing organization, we found that IOs had better referencing practices than GMCFs. Our findings call into question the evidence-base behind the reports published by these policy actors. We emphasize the need to rely on strong academic literature to inform policy decisions around the future of work.

The heightened risk of global warming has attracted the special attention of researchers and policymakers towards the linkage between economic growth and environmental protection. Thus, this study examines the effects of FDI inflow, GDP, trade openness, urbanisation level, and nuclear energy consumption on environmental pollution factor CO2 emissions by using the STIRPAT model (1997). Furthermore, this study also examines the moderating role of green financing by analysing the data of eight nuclear power states from 2008 to 2019. The results revealed that foreign direct investment, gross domestic product, and urbanisation as increased contributors to CO2 emissions, thus damaging the environment. Whereas trade openness, nuclear energy consumption, and green financing have an inverse relation with CO2 which means they positively contribute to the environment of the nuclear power states. The outcomes also reveal that green financing negatively moderates the relationships and positively contributes toward environmental safety (reduces CO2). The findings have paved the way for the regulators to increase their focus on green finance to play a positive role in environment preservation and conservation alongside economic growth. Not only that, but the results also imply that the policymakers should direct their efforts to promote nuclear energy production and consumption to cater to the surging energy needs.

Hypoplastic left heart syndrome is abnormal development of left sided cardiac structure, leading to obstruction to blood flow from the left ventricular outflow tract. We are presenting a case of primigravida with 35weeks period of gestation with gestational hypertension with left hypoplastic heart syndrome with single umbilical artery which was diagnosed at 24weeks anomaly scan but she continued the pregnancy. Emergency caesarean section was done and a live male baby was delivered but shifted to NICU in view of antenatally diagnosed hypoplastic left heart syndrome. Baby was discharged on day 8 of life, on day 21 of life baby presented with gasping breaths. Chest x-ray showed extensive infiltrates and baby died due to pneumonia and cardiac arrest.