Mathematical discoveries from program search with large language models.

Large language models (LLMs) have demonstrated tremendous capabilities in solving complex tasks, from quantitative reasoning to understanding natural language. However, LLMs sometimes suffer from confabulations (or hallucinations), which can result in them making plausible but incorrect statements1,2. This hinders the use of current large models in scientific discovery. Here we introduce FunSearch (short for searching in the function space), an evolutionary procedure based on pairing a pretrained LLM with a systematic evaluator. We demonstrate the effectiveness of this approach to surpass the best-known results in important problems, pushing the boundary of existing LLM-based approaches3. Applying FunSearch to a central problem in extremal combinatorics-the cap set problem-we discover new constructions of large cap sets going beyond the best-known ones, both in finite dimensional and asymptotic cases. This shows that it is possible to make discoveries for established open problems using LLMs. We showcase the generality of FunSearch by applying it to an algorithmic problem, online bin packing, finding new heuristics that improve on widely used baselines. In contrast to most computer search approaches, FunSearch searches for programs that describe how to solve a problem, rather than what the solution is. Beyond being an effective and scalable strategy, discovered programs tend to be more interpretable than raw solutions, enabling feedback loops between domain experts and FunSearch, and the deployment of such programs in real-world applications.

Enteric viruses replicate in salivary glands and infect through saliva.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

Prospects for the convergence of polyphenols with pharmaceutical drugs in Type 2 Diabetes: challenges, risks, and strategies.

Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to a variety of life-threatening secondary health conditions. Current treatment strategies primarily revolve around tight glucose control that is difficult to achieve and often turns out to be dangerous due to possible hypoglycemic events. Numerous long-term studies have demonstrated that complex pathways, including low-grade inflammation due to fluctuating glucose levels, are involved in the progression of the disease and the development of secondary health conditions. Growing clinical evidence supports the effectiveness of using multiple medications, possibly in combination with insulin, to effectively manage T2DM. On the other hand, despite the huge, largely untapped potential therapeutic benefit of 'polyphenols', there remains a general skepticism of the practice. However, for any evidence-based clinical intervention, the balance of benefits and risks takes center stage and is governed by biopharmaceutics principles. In this article, we outline the current clinical perspectives on pharmaceutical drug combinations, rationale for early initiation of insulin, and the advantages of novel dosage forms to meet the pathophysiological changes of T2DM, emphasizing the need for further clinical studies to substantiate these approaches. We also make the case for traditional medicines and their combinations with pharmaceutical drugs and outline the inherent challenges in doing so, while also providing recommendations for future research and clinical practice. Significance Statement Type 2 diabetes is associated with life-threatening secondary health conditions that are often difficult to treat. This review provides an in-depth account of preventing/delaying secondary health conditions through combination therapies and emphasizes the role of effective delivery strategies in realizing the translation of such combinations. We will build the case for the importance of polyphenols in diabetes, determine the reasons for skepticism, and potential combinations with pharmaceutical drugs.

Leveraging Lymphatic System Targeting in Systemic Lupus Erythematosus for Improved Clinical Outcomes.

The role of advanced drug delivery strategies in drug repositioning and minimizing drug attrition rates, when applied early in drug discovery, is poised to increase the translational impact of various therapeutic strategies in disease prevention and treatment. In this context, drug delivery to the lymphatic system is gaining prominence not only to improve the systemic bioavailability of various pharmaceutical drugs but also to target certain specific diseases associated with the lymphatic system. Although the role of the lymphatic system in lupus is known, very little is done to target drugs to yield improved clinical benefits. In this review, we discuss recent advances in drug delivery strategies to treat lupus, the various routes of drug administration leading to improved lymph node bioavailability, and the available technologies applied in other areas that can be adapted to lupus treatment. Moreover, this review also presents some recent findings that demonstrate the promise of lymphatic targeting in a preclinical setting, offering renewed hope for certain pharmaceutical drugs that are limited by efficacy in their conventional dosage forms. These findings underscore the potential and feasibility of such lymphatic drug-targeting approaches to enhance therapeutic efficacy in lupus and minimize off-target effects of the pharmaceutical drugs. SIGNIFICANCE STATEMENT: The World Health Organization estimates that there are currently 5 million humans living with some form of lupus. With limited success in lupus drug discovery, turning to effective delivery strategies with existing drug molecules, as well as those in the early stage of discovery, could lead to better clinical outcomes. After all, effective delivery strategies have been proven to improve treatment outcomes.

Electrical switching of magnetic order in an orbital Chern insulator.

Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields-a longstanding technological goal in spintronics and multiferroics1,2-can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator3-6, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered7-14. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands15-17. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects18 with transverse resistance approximately equal to h/2e2 (where h is Planck's constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis19 indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.

Dengue Infection During Pregnancy and Adverse Birth Outcomes: A Systematic Review and Meta-Analysis.

Dengue is a rapidly spreading mosquito-borne viral disease, posing significant public health challenges in tropical and subtropical regions. This systematic review and meta-analysis aimed to evaluate the relationship between maternal dengue virus infection and adverse birth outcomes. A literature search was conducted in PubMed, Embase, and web of science databases until April 2024. Observational studies examining the association between laboratory-confirmed maternal dengue infection and adverse birth outcomes such as preterm birth, low birth weight (LBW), small for gestational age (SGA), stillbirth, and postpartum haemorrhage were included. Data were extracted, and risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to pool data in R software (V 4.3). Twenty studies met the inclusion criteria. The pooled prevalence of preterm birth among dengue-affected pregnancies was 18.3% (95% CI: 12.6%-25.8%), with an OR of 1.21 (95% CI: 0.78-1.89). For LBW, the pooled prevalence was 17.1% (95% CI: 10.4%-26.6%), with an OR of 1.00 (95% CI: 0.69-1.41). SGA had a pooled prevalence of 11.2% (95% CI: 2.7%-36.9%) and an OR of 0.93 (95% CI: 0.41-2.14). The prevalence of stillbirth was 3.3% (95% CI: 1.6%-6.8%), with significant associations found in some studies (RR: 2.67; 95% CI: 1.09-6.57). Postpartum haemorrhage had an OR of 1.97 (95% CI: 0.53-2.69). While maternal dengue infection was associated with a higher prevalence of preterm birth and LBW, the associations were not statistically significant. Significant associations were observed for stillbirth in specific studies. Further research with standardized methodologies is needed to clarify these relationships and identify potential mechanisms.

Risk of cognitive decline among patients with dengue virus infection: A systematic review.

BACKGROUND: Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer's disease, memory loss, and confusion. METHODS: This systematic review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale. RESULTS: Of the 1,129 articles identified, five were included in the review, covering a total of 200,873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer's disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear. CONCLUSION: This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health.

Estimation of burden of cancer incidence and mortality in India: based on global burden of disease study 1990-2021.

BACKGROUND: Cancer poses a significant public health challenge in India, making it crucial to predict its future impact for effective healthcare planning. This study forecast cancer incidence, mortality, and disability-adjusted life years (DALYs) in India from 2022 to 2031. METHODS: We extracted age-standardized data on incidence, prevalence, DALYs, and mortality from 1990 to 2021 from the Global Burden of Disease (GBD) study. We used Decadal Average Percentage Change techniques to identify trends in cancer burden over decades and the Autoregressive Integrated Moving Average (ARIMA) method were used for forecasting. The ARIMA (2,2,2) model was identified as the best for predicting cancer incidence, ARIMA (0,3,3) for DALYs, and ARIMA (0,2,2) for mortality. RESULTS: The cancer incidence rate is expected to rise from 529.40 (95% CI: 525.41-533.38) in 2022 to 549.17 (95% CI: 487.43-610.92) per 100,000 population in 2031. The DALYs rate is projected to decrease from 2001.53 (95% CI: 1964.24-2038.82) in 2022 to 1842.08 (95% CI: 1273.57-2410.60) per 100,000 population in 2031, indicating improvements in cancer burden management. Mortality rates are forecasted to increase slightly, from 71.52 (95% CI: 69.91-73.12) in 2022 to 73.00 (95% CI: 60.88-85.11) per 100,000 population in 2031. Overall, while incidence and mortality rates show a slight upward trend, the DALYs rate is projected to decrease, reflecting potential advancements in cancer management and treatment over the forecast period. CONCLUSIONS: Over the next decade, cancer incidence and mortality are expected to increase in India, highlighting the need for enhanced prevention, early detection, and proper treatment strategies. Despite these increases, the anticipated decrease in DALYs suggests potential advancements in cancer management, warranting further investigation into the drivers of this positive trend and measures to sustain it.

An Updated Review Summarizing the Anticancer Potential of Poly(Lactic-co-Glycolic Acid) (PLGA) Based Curcumin, Epigallocatechin Gallate, and Resveratrol Nanocarriers.

The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds.

Predictors of acute kidney injury in dengue patients: a systematic review and meta-analysis.

BACKGROUND: Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI's impact. METHODS: We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. RESULTS: Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02-3.42), male gender (OR: 3.13, 95% CI: 1.82-4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274-6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42-11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. CONCLUSION: Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes.

Exploration of culturable bacterial associates of aphids and their interactions with entomopathogens.

Aphids shelter several bacteria that benefit them in various ways. The associates having an obligatory relationship are non-culturable, while a few of facultative associates are culturable in insect cell lines, axenic media or standard microbiology media. In the present investigation, isolation, and characterization of the culturable bacterial associates of various aphid species, viz., Rhopalosiphum maidis, Rhopalosiphum padi, Sitobion avenae, Schizaphis graminum, and Lipaphis erysimi pseudobrassicae were carried out. A total of 42 isolates were isolated using different growth media, followed by their morphological, biochemical, and molecular characterization. The isolated culturable bacterial associates were found to belong to the genera Acinetobacter, Bacillus, Brevundimonas, Cytobacillus, Fictibacillus, Planococcus, Priestia, Pseudomonas, Staphylococcus, Sutcliffiella, and Tumebacillus which were grouped under seven families of four different orders of phyla Bacillota (Firmicutes) and Pseudomonata (Proteobacteria). Symbiont-entomopathogen interaction study was also conducted, in which the quantification of colony forming units of culturable bacterial associates of entomopathogenic fungal-treated aphids led us to the assumption that the bacterial load in aphid body can be altered by the application of entomopathogens. Whereas, the mycelial growth of entomopathogens Akanthomyces lecanii and Metarhizium anisopliae was found uninhibited by the bacterial associates obtained from Sitobion avenae and Rhopalosiphum padi. Analyzing persistent aphid microflora and their interactions with entomopathogens enhances our understanding of aphid resistance. It also fosters the development of innovative solutions for agricultural pest management, highlighting the intricate dynamics of symbiotic relationships in pest management strategies.

Effect of rotational shear on the dielectric dispersion of a nematic liquid crystal above the Freedericksz threshold field.

Rheo-dielectric studies of soft materials provide important information on the dynamic structure and electric polarization. We study the dielectric dispersion of a nematic liquid crystal by applying a high AC probe field without a DC bias and a low AC probe field with a high DC bias under steady rotational shear. The dielectric anisotropy of the nematic is positive and the applied electric field is parallel to the velocity gradient with a magnitude larger than the Freedericksz threshold field. We find that the dielectric dispersion and the relaxation frequencies are strongly shear rate dependent. The analysis of the results based on a simple physical model shows that the effective dielectric constant of the nematic with non-uniform director tilt in the shear plane can be modelled as a series combination of parallel and perpendicular components. Our experiments demonstrate changes in dielectric dispersion are due to molecular reorientation under the influence of the competing effects of hydrodynamic and dielectric torques.

Probing of plant transcriptomes reveals the hidden genetic diversity of the family Secoviridae.

Secoviruses are single-stranded RNA viruses that infect plants. In the present study, we identified 61 putative novel secoviral genomes in various plant species by mining publicly available plant transcriptome data. These viral sequences represent the genomes of 13 monopartite and 48 bipartite secovirids. The genome sequences of 52 secovirids were coding-complete, and nine were partial. Except for small open reading frames (ORFs) determined in waikaviral genomes and RNA2 of torradoviruses, all of the recovered genomes/genome segments contained a large ORF encoding a polyprotein. Based on genome organization and phylogeny, all but three of the novel secoviruses were assigned to different genera. The genome organization of two identified waika-like viruses resembled that of the recently identified waika-like virus Triticum aestivum secovirus. Phylogenetic analysis revealed a pattern of host-virus co-evolution in a few waika- and waika-like viruses and increased phylogenetic diversity of nepoviruses. The study provides a basis for further investigation of the biological properties of these novel secoviruses.

Effectiveness of early Anakinra on cardiac function in children with multisystem inflammatory syndrome of COVID-19: a systematic review.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C. METHODS: A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra's role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements. CONCLUSION: Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra's effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols.

Ayurveda therapy in the management of epilepsy.

Epilepsy, a chronic non-communicable disease of the brain, is one of the most common neurological diseases globally that affects people of all ages. The existence of medical, neurological, psychiatric, and cognitive comorbidities has always undermined the available advanced treatment strategies for epilepsy. New-generation antiepileptic drugs being less successful in completely controlling the seizures and observance of complex diseases, including drug-resistant cases, have provided scope for integrating and incorporating the therapeutic modalities of Ayurveda, the ancient Indian art of holistic medicine, in the effective management of epilepsy. Epilepsy can be correlated to Apasmara, described in the classics of Ayurveda as the transient appearance of unconsciousness with loathsome expression due to derangement of memory, intelligence, and mind. The multifaceted therapeutic approach of Ayurveda, which involves pharmacologic and nonpharmacologic measures, purificatory and pacifying procedures, herbal and herbo-mineral formulations, disease, and host-specific approaches, have enhanced the potential of not only relieving symptoms but also modifying the pathophysiology of the disease. Newer paradigms of research in Ayurveda, along with holistic and integrative approaches with contemporary medicine, can not only benefit the existing healthcare system but also impact future healthcare management in epileptology research. This cursory literature review is an earnest attempt to identify, evaluate, and summarize various studies and provide a comprehensive insight into the potential of Ayurveda in understanding and treating epilepsy.

Artificial intelligence for discrimination of Crohn's disease and gastrointestinal tuberculosis: A systematic review.

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.

A high-performance flexible humidity sensor based on a TiO2-MWCNT nanocomposite for human healthcare applications.

The present work shows the improved humidity sensing characteristics of TiO2 nanoparticles in the form of a nanocomposite with multiwalled carbon nanotubes (MWCNTs) prepared by a hydration-dehydration method. The structural and morphological characterizations of TiO2-MWCNTs confirm the nanocomposite formation without any other impurities and with an improved surface area. The pure TiO2 and nanocomposite films are deposited on IDE coated flexible poly-ethylene terephthalate (PET) substrates by a drop casting method. The nanocomposite shows improved sensitivity (1246.2 MΩ/%RH) and an ultrafast response/recovery time (2 s/1 s) with a minimal hysteresis of 0.27%RH. Further, the flexible nanocomposite sensor is tested for human healthcare applications including respiratory monitoring, apnea like situations, and skin moisture detection. The sensor can distinguish different breath patterns like normal, fast, deep and apnea like situations significantly. Skin moisture detection can also be performed using the nanocomposite sensor in a non-invasive manner. Overall, this study represents an environmentally friendly, easy to fabricate, flexible TiO2-MWCNT nanocomposite based improved humidity sensor for application in human healthcare and wearable devices.

Epithelial-mesenchymal transition in chemoradiation-induced lung damage: Mechanisms and potential treatment approaches.

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.

Adrenocortical suppression in children with nephrotic syndrome treated with corticosteroids.

BACKGROUND: Children with nephrotic syndrome are exposed to alternate day steroids for prolonged periods and this poses the need for evaluation of adrenocortical suppression using the adrenocorticotropic hormone (ACTH) stimulation test. METHODS: This cross-sectional study enrolled children (2-18 years) both with steroid sensitive nephrotic syndrome (SSNS) (n = 27) and steroid resistant (SRNS) (n = 25); those on daily prednisolone or having serious bacterial infections or hospitalized were excluded. The primary objective was to determine prevalence of adrenocortical suppression in those on low dose alternate day steroids for more than 8 weeks or having received > 2 mg/kg/d for > 2 weeks in the past 1 year and currently in remission. A baseline morning fasting sample of serum cortisol was taken and 25 IU of ACTH (Acton Prolongatum*) injected intramuscularly and repeat serum cortisol sample taken after 1 h. All patients with 1 h post ACTH cortisol < 18.0 µgm/dl were diagnosed with adrenal insufficiency. Receiver operating characteristic curve was drawn to predict the prednisolone dose for adrenal insufficiency. RESULTS: Fifty-two (33 males) children were enrolled (mean age 9.4 years); proportion of adrenal insufficiency was 50% and 64% using baseline and post stimulation cutoffs. The total cumulative annual dose of prednisolone 0.22 mg/kg/day predicted adrenocortical suppression with AUC 0.76 (95% CI 0.63-0.89), with sensitivity of 63.9% and specificity of 81.3%. CONCLUSIONS: A significant proportion of children with nephrotic syndrome were detected with adrenal insufficiency on ACTH stimulation test. A cumulative steroid intake of > 0.22 mg/kg/day on an alternate day basis emerged as a risk factor for predicting adrenocortical suppression.

Zinc oxide nanoflakes supported copper oxide nanosheets as a bifunctional electrocatalyst for OER and HER in an alkaline medium.

Bifunctional electrocatalysts are the attractive research in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in the overall water-splitting reactions. The design and development of the cost-effective OER/HER bifunctional electrocatalysts with superior catalytic activity are still remaining as the big challenges. Herein, we have developed the CuO-ZnO nanocomposite as a bifunctional OER/HER electrocatalyst via simple chemical precipitation method. The nanocomposite was investigated for its crystalline structure, surface morphology and the functions of elements using XRD, FT-IR, SEM, TEM and XPS characterization techniques, respectively. The nanocomposite exhibited the excellent activity for the overall water-splitting in an alkaline medium. The CuO-ZnO nanocomposite showed the less onset potential of 1.4 and 0.15 V versus RHE in 1M KOH (Tafel slopes value of 0.180 and 0.400 V dec-1) for OER and HER, respectively. Hence, the as-prepared bifunctional electrocatalyst displayed the high stability for 10 h in the water electrolysis processes.