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Highlights Dielectric CaCu 3 Ti 4 O 12 (CCTO) was used as electrolyte in low-temperature solid oxide fuel cells for the first time. A new heterostructure electrolyte was designed based on CCTO and Ni 0.8 Co 0.15 Al 0.05 LiO 2− δ (NCAL). Promising ionic conductivity and high fuel cell performance were achieved CCTO–NCAL realized an electrolyte function due to its good dielectric property and a heterojunction effect. The development of low-temperature solid oxide fuel cells (LT-SOFCs) is of significant importance for realizing the widespread application of SOFCs. This has stimulated a substantial materials research effort in developing high oxide-ion conductivity in the electrolyte layer of SOFCs. In this context, for the first time, a dielectric material, CaCu 3 Ti 4 O 12 (CCTO) is designed for LT-SOFCs electrolyte application in this study. Both individual CCTO and its heterostructure materials with a p -type Ni 0.8 Co 0.15 Al 0.05 LiO 2− δ (NCAL) semiconductor are evaluated as alternative electrolytes in LT-SOFC at 450–550 °C. The single cell with the individual CCTO electrolyte exhibits a power output of approximately 263 mW cm −2 and an open-circuit voltage (OCV) of 0.95 V at 550 °C, while the cell with the CCTO–NCAL heterostructure electrolyte capably delivers an improved power output of approximately 605 mW cm −2 along with a higher OCV over 1.0 V, which indicates the introduction of high hole-conducting NCAL into the CCTO could enhance the cell performance rather than inducing any potential short-circuiting risk. It is found that these promising outcomes are due to the interplay of the dielectric material, its structure, and overall properties that led to improve electrochemical mechanism in CCTO–NCAL. Furthermore, density functional theory calculations provide the detailed information about the electronic and structural properties of the CCTO and NCAL and their heterostructure CCTO–NCAL. Our study thus provides a new approach for developing new advanced electrolytes for LT-SOFCs.

Computer vision has become increasingly important and effective in recent years due to its wide-ranging applications in areas as diverse as smart surveillance and monitoring, health and medicine, sports and recreation, robotics, drones, and self-driving cars. Visual recognition tasks, such as image classification, localization, and detection, are the core building blocks of many of these applications, and recent developments in Convolutional Neural Networks (CNNs) have led to outstanding performance in these state-of-the-art visual recognition tasks and systems. As a result, CNNs now form the crux of deep learning algorithms in computer vision. This self-contained guide will benefit those who seek to both understand the theory behind CNNs and to gain hands-on experience on the application of CNNs in computer vision. It provides a comprehensive introduction to CNNs starting with the essential concepts behind neural networks: training, regularization, and optimization of CNNs. The book also discusses a wide range of loss functions, network layers, and popular CNN architectures, reviews the different techniques for the evaluation of CNNs, and presents some popular CNN tools and libraries that are commonly used in computer vision. Further, this text describes and discusses case studies that are related to the application of CNN in computer vision, including image classification, object detection, semantic segmentation, scene understanding, and image generation. This book is ideal for undergraduate and graduate students, as no prior background knowledge in the field is required to follow the material, as well as new researchers, developers, engineers, and practitioners who are interested in gaining a quick understanding of CNN models.

The tumor immune response is in a dynamic balance between antitumor mechanisms, which serve to decrease cancer growth, and the protumor inflammatory response, which increases immune tolerance, cell survival, and proliferation. Hypoxia and expression of HIF-1α and HIF-2α are characteristic features of all solid tumors. HIF signaling serves as a major adaptive mechanism in tumor growth in a hypoxic microenvironment. HIFs represent a critical signaling node in the switch to protumorigenic inflammatory responses through recruitment of protumor immune cells and altered immune cell effector functions to suppress antitumor immune responses and promote tumor growth through direct growth-promoting cytokine production, angiogenesis, and ROS production. Modulating HIF function will be an important mechanism to dampen the tumor-promoting inflammatory response and inhibit cancer growth.

Acute Coronavirus Disease 2019 (COVID-19) has been associated with new-onset cardiovascular disease (CVD) and diabetes mellitus (DM), but it is not known whether COVID-19 has long-term impacts on cardiometabolic outcomes. This study aimed to determine whether the incidence of new DM and CVDs are increased over 12 months after COVID-19 compared with matched controls. We conducted a cohort study from 2020 to 2021 analysing electronic records for 1,356 United Kingdom family practices with a population of 13.4 million. Participants were 428,650 COVID-19 patients without DM or CVD who were individually matched with 428,650 control patients on age, sex, and family practice and followed up to January 2022. Outcomes were incidence of DM and CVD. A difference-in-difference analysis estimated the net effect of COVID-19 allowing for baseline differences, age, ethnicity, smoking, body mass index (BMI), systolic blood pressure, Charlson score, index month, and matched set. Follow-up time was divided into 4 weeks from index date (\"acute COVID-19\"), 5 to 12 weeks from index date (\"post-acute COVID-19\"), and 13 to 52 weeks from index date (\"long COVID-19\"). Net incidence of DM increased in the first 4 weeks after COVID-19 (adjusted rate ratio, RR 1.81, 95% confidence interval (CI) 1.51 to 2.19) and remained elevated from 5 to 12 weeks (RR 1.27, 1.11 to 1.46) but not from 13 to 52 weeks overall (1.07, 0.99 to 1.16). Acute COVID-19 was associated with net increased CVD incidence (5.82, 4.82 to 7.03) including pulmonary embolism (RR 11.51, 7.07 to 18.73), atrial arrythmias (6.44, 4.17 to 9.96), and venous thromboses (5.43, 3.27 to 9.01). CVD incidence declined from 5 to 12 weeks (RR 1.49, 1.28 to 1.73) and showed a net decrease from 13 to 52 weeks (0.80, 0.73 to 0.88). The analyses were based on health records data and participants' exposure and outcome status might have been misclassified. In this study, we found that CVD was increased early after COVID-19 mainly from pulmonary embolism, atrial arrhythmias, and venous thromboses. DM incidence remained elevated for at least 12 weeks following COVID-19 before declining. People without preexisting CVD or DM who suffer from COVID-19 do not appear to have a long-term increase in incidence of these conditions.

Background:Reproductive health represents a complex challenge to rheumatologists treating women with chronic autoimmune diseases. To date, there are no studies from India that have evaluated the perceptions and practices of rheumatologists about various areas of reproductive health such as sexual health, contraception, family planning, and infertility in women of reproductive age group. There is a dilemma regarding the appropriate time to address such issues and there are various challenges faced by the doctors in addressing these due to various psychosocial barriers from the patients.Objectives:To assess whether current clinical practice routinely provides adequate response, care and counselling to alleviate concerns regarding sexual and reproductive health care in women with Autoimmune Rheumatic Diseases.Methods:A questionnaire assessing the perception and varied practices of rheumatologists to address topics like sexual dysfunction, contraception, family planning and infertility, pregnancy, and drug teratogenicity in women with autoimmune rheumatic diseases was devised as Google form and was distributed in person and via social media channels across the country. A total of 130 rheumatologists filled out the questionnaire. Data was coded and recorded in MS Excel spreadsheet program. SPSS v23 (IBM Corp.) was used for data analysis Descriptive statistics were elaborated in the form of means/standard deviations, medians/IQRs for continuous variables, and frequencies and percentages for categorical variables.Results:The mean Age (Years± SD) of rheumatologists was 44.19 ± 11.32 and 71.5% of doctors were male. 43.8% of the rheumatologists practiced for more than 10 years and 30% practiced in multiple institutions. 92.3% of rheumatologists belived that reproductive health is an important aspect of women with AIRD and concerns regarding it should be discussed by them. The time spent for discussion was highest for teratogenic drugs followed by family planning and unplanned pregnancies. The least time was spent on Sexual Health and Infertility. 69.2% of rheumatologists believed in discussing these topics at the time of diagnosis and 93.1% revisited these topics over time. 64.4 % of rheumatologists stated that they discuss these concerns with both patient and their partners. The most common barrier identified by doctors while discussing reproductive health was insufficient time during the consultation followed by the preference of a female rheumatologist by the patients. When asked whether other specialties unilaterally make decisions related to patient’s health, 52.4% of rheumatologists stated that the other teams refer patients back to them for any management-related decisions in context to their autoimmune disease. Also, when asked if they discussed concerns regarding reproductive health in AIRD with gynaecologist, 61.5% of rheumatologists seldom discussed these issues with a patient’s gynaecologist. However, 95.4% of Rheumatologists agreed upon a need for an interdisciplinary approach between them and obstetricians.Table 1.Figure 1.Conclusion:Our study illustrates a need for more holistic communication between rheumatologists and women of childbearing age with AIRDs in context to their reproductive health concerns. It is also important to have a consistent approach among rheumatologists in addressing various aspects of reproductive health care to ensure the standard of care and also to obtain better compliance. Rheumatologists need to explain to the patients the impact their disease can have on their sexual and reproductive health and vice versa. These concerns needs to be discussed with patient’s partner to ensure adequate knowledge regarding safe contraception during high disease burden and use of teratogenic drugs. There is an unmet need for a collaborative approach between rheumatologists and gynaecologists to lower the risk of sexual dysfunction, unplanned pregnancies, and bad obstetric outcomes. Also, patient-centred care should be incorporated into routine clinical practice and a standard consensus amongst relevant clinicians is needed to address all of the above and remove barriers from shared decision-making in such patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

COVID-19 is a disease with unique characteristics that include lung thrombosis 1 , frequent diarrhoea 2 , abnormal activation of the inflammatory response 3 and rapid deterioration of lung function consistent with alveolar oedema 4 . The pathological substrate for these findings remains unknown. Here we show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation. The generation of these syncytia results from activation of the SARS-CoV-2 spike protein at the cell plasma membrane level. On the basis of these observations, we performed two high-content microscopy-based screenings with more than 3,000 approved drugs to search for inhibitors of spike-driven syncytia. We converged on the identification of 83 drugs that inhibited spike-mediated cell fusion, several of which belonged to defined pharmacological classes. We focused our attention on effective drugs that also protected against virus replication and associated cytopathicity. One of the most effective molecules was the antihelminthic drug niclosamide, which markedly blunted calcium oscillations and membrane conductance in spike-expressing cells by suppressing the activity of TMEM16F (also known as anoctamin 6), a calcium-activated ion channel and scramblase that is responsible for exposure of phosphatidylserine on the cell surface. These findings suggest a potential mechanism for COVID-19 disease pathogenesis and support the repurposing of niclosamide for therapy. Lungs from patients who died from COVID-19 show atypical fused cells, the formation of which is mediated by the SARS-CoV-2 spike protein, and drugs that inhibit TMEM16F can prevent spike-induced syncytia formation.

Key Points Peroxisome proliferator-activated receptors (PPARs) have central roles in the regulation of glucose and lipid homeostasis through their functions as molecular sensors that respond to endogenous ligands, leading to the modulation of gene expression. PPARs also regulate cell proliferation, differentiation and inflammation. PPARα mediates hepatocarcinogenesis induced by long-term administration of PPARα agonists in rodent models, an effect that is not found in humans. The mechanism underlying species-specific hepatocarcinogenesis is through mouse PPARα-dependent regulation of the let-7c microRNA, which leads to increased expression of the oncoprotein MYC. The current interest in targeting PPARα for the prevention of certain cancers, including colon and leukaemia, is based on studies showing that PPARα agonists inhibit the proliferation of endothelial cells, increase the synthesis of PPARγ agonists and potentially interfere with the Warburg effect. The role of PPARβ/δ in carcinogenesis is controversial. Several studies have shown that PPARβ/δ is upregulated in cancer cells by the adenomatous polyposis coli (APC)–β-catenin–TCF4 pathway and has a pro-tumorigenic effect in many cancer types. However, other studies have shown that PPARβ/δ agonists can induce terminal differentiation and inhibit innate inflammation, suggesting anticancer effects. In addition, a retrospective study has shown that low expression levels of PPARβ/δ are associated with the decreased survival of patients with colorectal cancer. Therefore, there remains a need to further examine PPARβ/δ protein expression patterns quantitatively in tumour models and the putative mechanisms that are mediated by PPARβ/δ agonists associated with anti-apoptotic or growth stimulatory effects. PPARγ agonists can induce terminal differentiation, inhibit cell proliferation, promote apoptosis and inhibit innate inflammation in many cancer models. This has led to a number of clinical trials with PPARγ agonists, but these have generated mixed results. Moreover, some PPARγ agonists have been associated with pro-tumorigenic effects. Emerging evidence indicates that targeting PPARγ in combination with other chemopreventive or chemotherapeutic agents might increase the efficacy of the effects that are induced by monotherapies. Owing to similarities in the abilities of the three PPARs to improve different metabolic disorders that are known to be associated with increased cancer risk (such as diabetes, obesity, dyslipidemias and chronic inflammation), modulating the activities of the PPARs remains an attractive approach for the treatment and prevention of cancer. The challenge is to advance the discovery of molecular mechanisms of action in order to identify and characterize effective PPAR agonists with acceptable safety profiles. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. This Review discusses the roles of PPARs in cancer and focuses on PPARβ/δ and the controversies yet to be resolved. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. Although all of these functions might contribute to the influence of PPARs in carcinogenesis, there is a distinct need for a review of the literature and additional experimentation to determine the potential for targeting PPARs for cancer therapy and cancer chemoprevention. As PPAR agonists include drugs that are used for the treatment of metabolic diseases, a more complete understanding of the roles of PPARs in cancer will aid in determining any increased cancer risk for patients undergoing therapy with PPAR agonists.

Chronic heart failure continues to impose a substantial health-care burden, despite recent treatment advances. The key pathophysiological process that ultimately leads to chronic heart failure is cardiac remodelling in response to chronic disease stresses. Here, we review recent advances in our understanding of molecular and cellular mechanisms that play a part in the complex remodelling process, with a focus on key molecules and pathways that might be suitable targets for therapeutic manipulation. Such pathways include those that regulate cardiac myocyte hypertrophy, calcium homoeostasis, energetics, and cell survival, and processes that take place outside the cardiac myocyte—eg, in the myocardial vasculature and extracellular matrix. We also discuss major gaps in our current understanding, take a critical look at conventional approaches to target discovery that have been used to date, and consider new investigational avenues that might accelerate clinically relevant discovery.

Articular cartilage is an avascular tissue, with limited ability to repair and self-renew. Defects in articular cartilage can induce debilitating degenerative joint diseases such as osteoarthritis. Currently, clinical treatments have limited ability to repair, for they often result in the formation of mechanically inferior cartilage. In this review, we discuss the factors that affect cartilage homeostasis and function, and describe the emerging regenerative approaches that are informing the future treatment options.