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Introduction: In recent times, there has been an increased number of published materials related to artificial intelligence (AI) in both the medical field, and specifically, in the domain of neurosurgery. Studies integrating AI into neurosurgical practice suggest an ongoing shift towards a greater dependence on AI-assisted tools for diagnostics, image analysis, and decision-making. Material and methods: The study evaluated the performance of ChatGPT-3.5 and ChatGPT-4 on a neurosurgery exam from Autumn 2017, which was the latest exam with officially provided answers on the Medical Examinations Center in Łódź, Poland (Centrum Egzaminów Medycznych – CEM) website. The passing score for the National Specialization Exam (Państwowy Egzamin Specjalizacyjny – PES) in Poland, as administered by CEM, is 56% of the valid questions. This exam, chosen from CEM, comprised 116 single-choice questions after eliminating four outdated questions. These questions were categorized into ten thematic groups based on the subjects they address. For data collection, both ChatGPT versions were briefed on the exam rules and asked to rate their confidence in each answer on a scale from 1 (definitely not sure) to 5 (definitely sure). All the interactions were conducted in Polish and were recorded. Results: ChatGPT-4 significantly outperformed ChatGPT-3.5, showing a notable improvement with a 29.4% margin (p < 0.001). Unlike ChatGPT-3.5, ChatGPT-4 successfully reached the passing threshold for the PES. ChatGPT-3.5 and ChatGPT-4 had the same answers in 61 questions (52.58%), both were correct in 28 questions (24.14%), and were incorrect in 33 questions (28.45%). Conclusions: ChatGPT-4 shows improved accuracy over ChatGPT-3.5, likely due to advanced algorithms and a broader training dataset, highlighting its better grasp of complex neurosurgical concepts.

Understanding the evolutionary mechanisms underlying the maintenance of individual differences in behavior and physiology is a fundamental goal in ecology and evolution. The pace-of-life syndrome hypothesis is often invoked to explain the maintenance of such within-population variation. This hypothesis predicts that behavioral traits are part of a suite of correlated traits that collectively determine an individual's propensity to prioritize reproduction or survival. A key assumption of this hypothesis is that these traits are underpinned by genetic trade-offs among life-history traits: genetic variants that increase fertility, reproduction and growth might also reduce lifespan. We performed a systematic literature review and meta-analysis to summarize the evidence for the existence of genetic trade-offs between five key life-history traits: survival, growth rate, body size, maturation rate, and fertility. Counter to our predictions, we found an overall positive genetic correlation between survival and other life-history traits and no evidence for any genetic correlations between the non-survival life-history traits. This finding was generally consistent across pairs of life-history traits, sexes, life stages, lab vs. field studies, and narrow- vs. broad-sense correlation estimates. Our study highlights that genetic trade-offs may not be as common, or at least not as easily quantifiable, in animals as often assumed.

Predation threat is a major driver of behavior in many prey species. Animals can recognize their relative risk of predation based on cues in the environment, including visual and/or chemical cues released by a predator or from its prey. When threat of predation is high, prey often respond by altering their behavior to reduce their probability of detection and/or capture. Here, we test how a clonal fish, the Amazon molly (Poecilia formosa), behaviorally responds to predation cues. We measured aggressive and social behaviors both under 'risk', where chemical cues from predatory fish and injured conspecifics were present, and control contexts (no risk cues present). We predicted that mollies would exhibit reduced aggression towards a simulated intruder and increased sociability under risk contexts as aggression might increase their visibility to a predator and shoaling should decrease their chance of capture through the dilution effect. As predicted, we found that Amazon mollies spent more time with a conspecific when risk cues were present, however they did not reduce their aggression. This highlights the general result of the 'safety in numbers' behavioral response that many small shoaling species exhibit, including these clonal fish, which suggests that mollies may view this response as a more effective anti-predator response compared to limiting their detectability by reducing aggressive conspecific interactions.

Abstract Predation risk is one of the most important factors generating behavioral differences among populations. In addition, recent attention focusses on predation as a potential driver of patterns of individual behavioral variation within prey populations. Previous studies provide mixed results, reporting either increased or decreased among-individual variation in response to risk. Here, we take an explicit developmental approach to documenting how among-individual variation develops over time in response to predator exposure, controlling for both genetic and experiential differences among individuals. We reared juveniles of naturally clonal Amazon mollies, Poecilia formosa, either with or without a predator visible during feedings over 4 weeks and analyzed activity during feedings, time spent feeding and number of visits to the feeding spot. (I) Predator-exposed fish did not differ from control fish in average feeding behavior, but they were less active during feeding trials. (II) In the absence of the predator, substantial changes in among-individual variation over time were detected: among-individual differences in feeding duration increased whereas differences in activity decreased, but there were no changes in feeder visits. In contrast, in the presence of a predator, among-individual variation in all three behaviors was stable over time and often lower compared to control conditions. Our work suggests that predation risk may have an overall stabilizing effect on the development of individual variation and that differences in predation risk may well lead to population-wide differences in among-individual behavioral variation.

Patagonian maras, rodents endemic to South America, are classified as a near-threatened species. Various factors affect their health including parasitic diseases. The aim of this study was to perform morphometric, molecular and phylogenetic characterisation of one such parasitic disease agent, the nematode Graphidioides affinis, specimens of which were found in captive Patagonian maras.

Integrated phenotypes, that is, correlated suites of traits, can impact both evolutionary and ecological processes. Similarly, phenotypic plasticity, or the ability of one genotype to generate multiple phenotypes, can act as both a facilitator and constraint on evolutionary processes. While there has been an increasing focus on correlated behavioural means (i.e. behavioural syndromes), less attention has been paid to how plasticity in different behavioural traits may be correlated. Such correlated behavioural plasticities are likely to affect evolution and ecology, although possibly in different ways. Here, we review key insights from three research fields, behavioural syndromes, phenotypic plasticity and integrated phenotypes to provide a conceptual framework to understand why, how and when plasticities of different behavioural traits may become correlated. In particular, the conditions under which plasticity and behavioural syndromes are predicted to be important are also where correlated behavioural plasticities are likely to have the strongest impacts. In this review, we define correlated behavioural plasticities, summarize the conditions that are likely to give rise to them and highlight testable predictions in an effort to spark targeted research into this important phenomenon. We also provide a worked example to highlight how studying correlated plasticity can yield important new insights.

In recent years the ketogenic diet (KD) has become more and more popular. This diet is used not only to reduce weight but also there are an increasingly amount of new researches with multiple possitives effects in some diseases, such as prevention in cardiovascular conditions, diabetes mellitus, obstructive sleep apnea syndrome, some types of cancers and psoriasis. This paper offers an overview of these various medical conditions in which ketogenic diet can be used. Furthermore we describe the mechanism and potential efficacy of the KD. The PubMed and Google Scholar databases were searched.

Understanding how ADHD affects sexual functioning is key to providing comprehensive care. This review looks into the current research on sexual health in people with ADHD, focusing on how common sexual dysfunction is, how ADHD symptoms might impact sexual behavior, and what role medications play. By summarizing the existing studies, this review aims to highlight what we don’t know yet and suggest future research to improve treatment and patient outcomes. The review covers literature related to sexual functioning in ADHD, particularly looking at connections to hypersexuality, paraphilias, and various sexual behaviors. A thorough search of electronic databases, including PubMed, PsycINFO, and Google Scholar, was conducted using relevant keywords such as 'ADHD,' 'hypersexuality,' 'paraphilias,' 'sexuality,' 'sexual behavior,' and 'sexual violence.' The study duration was 6 months. Common features of ADHD, such as impulsivity, poor impulse control, and difficulties with self-regulation, may contribute to risky sexual behaviors, compulsive sexual behavior, or the development of paraphilic interests. It's important for doctors dealing with ADHD in children to discuss sexual health as the patient nears adolescence and offer guidance on safe sex. Treatment should combine medication with therapy. Since impulsivity seems to play a big role in risky sexual behavior, making contraceptives readily available could be important for sexual health. Longitudinal studies are necessary to better understand the temporal relationships and progression of sexual behaviors and ADHD symptoms over time. Given the potential impact of ADHD on sexual behavior and functioning, healthcare providers should consider screening for ADHD in patients presenting with issues related to hypersexuality, paraphilias, or other sexual concerns.

Introduction Depression is increasingly recognized as a major global health issue, driven by neurobiological, genetic, and environmental factors. Despite extensive research, understanding depression remains challenging due to its complexity and the lack of biomarkers. Recent studies highlight a link between depression and metabolic disturbances, emphasizing the need for alternative therapeutic approaches. Purpose This review aims to explore the therapeutic potential of GLP-1 (glucagon-like peptide-1) in treating depression, focusing on its impact on neurogenesis, neuroinflammation, neurotransmitter imbalances, and synaptic dysfunction. Materials and Methods A systematic review was conducted by analyzing literature from databases such as PubMed and Google Scholar, covering studies from 2003 to 2024. The review focused on keywords related to GLP-1, depression, and diabetes. Description of the State of Knowledge This section discusses the neurobiological mechanisms of depression, including neuroinflammation, neurotransmitter imbalances, and impaired neurogenesis. It highlights the potential of GLP-1 agonists to address these issues and improve mood and cognitive function. Conclusion The review concludes that GLP-1 holds promise as a therapeutic target for depression. Beyond its metabolic roles, GLP-1 can influence brain regions involved in mood regulation, enhance neurogenesis, reduce neuroinflammation, and improve neurotransmitter balance. These effects suggest that GLP-1-based therapies could offer new treatment options for depression, potentially improving outcomes beyond traditional antidepressants.

We present a case report of a 55-year-old woman who had a femoral vein intravascular papillary endothelial hyperplasia that required excision of the mass and subsequent repair of the right femoral vein using her right anterior accessory saphenous vein. She first presented with findings of a non-occlusive deep vein thrombus. However, after 6 months of persistent and enlarging mass with subsequent intravascular component on a follow-up duplex scan, a decision was made to bring her to the operating room for exploration and excision.

Breast cancer is the most common neoplasma affecting women. Over, the past few years, the incidence of breast cancer has significantly increased, including among young women. Hormone receptor-positive (HR+) Her2 negative (HER2-) early stage breast cancer can be successfully treated using the currently available treatment methods based on endocrine theraphy (ET). However, if we consider early stage breast cancer with high risk of recurrence or metastatic disease, endocrine therapy alone may be insufficient. Unfortunately, resistance to drugs is observed in both adjuvant and palliative endocrine therapy, therefore there is a need for new treatments that are both effective and less toxic than conventional chemotherapy. One of the most successful applications of this strategy has been the use of cyclin-dependent kinase (CDK) 4 and 6 inhibitors alongside endocrine therapy significantly enhance its effectiveness. This combination has been shown to substantially increase progression-free survival while maintaining relatively low levels of toxicity. One of them is abemaciclib, whose efficacy will be shown in this research work.

Bruxism, characterized by involuntary grinding or clenching of teeth, is a widespread condition with multifaceted implications for oral health, physical well-being, and quality of life. This comprehensive review aims to provide an in-depth study of bruxism, encompassing its definition, classification, etiology, pathophysiology, clinical manifestations, and consequences. Bruxism is classified based on its timing (sleep bruxism or awake bruxism). The etiology of bruxism is multifactorial, involving physiological factors such as central nervous system (CNS) pathways, sleep disorders, and occlusal factors, as well as psychological factors like stress, anxiety, personality traits and environmental factors including medications, substances, and stressors. Clinically, bruxism can result in various dental consequences, including tooth wear, fractures and damage to restorations, as well as temporomandibular disorders (TMDs) such as myofascial pain. These manifestations can negatively impact individual's oral health, physical well-being, and overall quality of life. Management strategies include behavioral and lifestyle changes, oral appliances, dental treatments for tooth damage, and, in certain instances, pharmacological interventions. While the current understanding of bruxism has advanced, further research is needed to fully elucidate its etiology, pathophysiology, and effective management strategies.

Introduction Poland has the largest shortage of nurses in Europe, as well as a low percentage of male nurses. Information relating to emotional intelligence has been explored to determine whether it predicts the characteristics and outcomes of qualified health professionals during their academic training and practice. Objective This study aimed to measure differences in emotional intelligence between male and female nursing students. Participants and methods In this cross-sectional study, emotional intelligence was measured using the Schutte Self-Report Emotional Intelligence Test (SSEIT) in 21 male and 127 female nursing students from John Paul II University in Biała Podlaska, Poland. Results The raw overall scores of emotional intelligence in male and female students were similar. Differences were observed after the conversion of raw scores into normalized (sten) scores. High normalized scores (sten 8–10) of emotional intelligence had every third of male students and only 14.2% of female students. The lowest sten values of emotional intelligence in male and female students were 3 and 1, respectively. Less than 10% of male students and over 20% of female students had low normalized scores (sten ≤3) for emotional intelligence and an isolated ability to recognize emotions (factor II). Conclusions The emotional intelligence expressed in normalized scores was higher in male nursing students than in female nursing students. This evidence may suggest that, at the stage of choosing a field of study, Polish male nursing students self-select for the nursing profession, at least in terms of emotional intelligence. The influx of men into the profession should be considered as a positive trend.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. It affects a large proportion of the general population leading to a negative effect on the quality of life. The pathophysiology of IBS is not fully known. There are several therapies currently used in the treatment of IBS. They vary from changing dietary habits to antibiotic therapy and must be personalized.

IntroductionSince boar spermatozoa show a marked deterioration in sperm quality when cooled, insemination doses are usually stored at 16–18 °C. However, maintaining this temperature during transport of semen doses is challenging, particularly during the summer months. An alternative could be to store the doses at 4 °C if cold-shock to the sperm could be prevented. The objective of this study was to evaluate boar sperm quality and fertility in in vitro fertilization after storage in AndroStar Premium at 4 °C for 1 week.MethodsInsemination doses (n = 9) in AndroStar Premium from a commercial boar semen collection station were transported to the laboratory at approximately 20 °C. At the laboratory, sperm quality evaluation and was preformed and each dose was split; half of each ejaculate was stored in a climate-controlled box at 16–18 °C, the other was slowly cooled to 4 °C. Both samples were stored for 1 week before further sperm quality evaluation and in vitro fertilization (IVF) were performed. Mean values were tested using generalized linear regression, with treatment and boar as fixed factors; p ≤ 0.05 was considered significant.ResultsSperm membrane integrity (mean ± sem: 91 ± 0.05 and 83 ± 0.09% for 16 and 4 °C, respectively) and superoxide production (6.79 ± 2.37 and 13.54 ± 6.23% for 16 and 4 °C, respectively), were different between treatments. The DNA fragmentation index was lower in cold-stored samples than in conventionally stored samples (3.74 ± 2.25 and 7.40 ± 3.36% for 4 and 16 °C, respectively). The numbers of oocytes developing to blastocyst on Day 6 (mean ± sd: 9.0 ± 8.0 and 6.0 ± 5.0%, for storage at 16 and 4 °C, respectively) were not different between treatments.DiscussionTherefore, storage of boar semen doses in AndroStar Premium at 4 °C for up to 7 days would be a viable alternative to current praxis.

Collective behaviours, such as flocking in birds or decision making by bee colonies, are some of the most intriguing behavioural phenomena in the animal kingdom. The study of collective behaviour focuses on the interactions between individuals within groups, which typically occur over close ranges and short timescales, and how these interactions drive larger scale properties such as group size, information transfer within groups and group-level decision making. To date, however, most studies have focused on snapshots, typically studying collective behaviour over short timescales up to minutes or hours. However, being a biological trait, much longer timescales are important in animal collective behaviour, particularly how individuals change over their lifetime (the domain of developmental biology) and how individuals change from one generation to the next (the domain of evolutionary biology). Here, we give an overview of collective behaviour across timescales from the short to the long, illustrating how a full understanding of this behaviour in animals requires much more research attention on its developmental and evolutionary biology. Our review forms the prologue of this special issue, which addresses and pushes forward understanding the development and evolution of collective behaviour, encouraging a new direction for collective behaviour research. This article is part of a discussion meeting issue 'Collective behaviour through time'.

PollinERA aims to reverse pollinator population declines and reduce the harmful impacts of pesticides. It addresses the call through four objectives: SO1 filling ecotoxicological data gaps to enable realistic prediction of the source and routes of exposure and impact of pesticides on pollinators and their sensitivity to individual pesticides and mixtures. SO2 developing and testing a co-monitoring scheme for pesticides and pollinators across European cropping systems and landscapes, developing risk indicators and mixture exposure information. SO3 developing models for predicting pesticide toxicological effects on pollinators for chemicals and organisms, environmental fate, toxicokinetic/ toxicodynamic, and population models. SO4 developing a population-level systems-based approach to risk and policy assessment considering multiple stressors and long-term spatiotemporal dynamics at the landscape scale and generating an open database for pollinator/pesticide data and tools.This will be achieved through developing knowledge and protocols for a broad range of toxicological testing, feeding to in silico models (QSARS, toxicokinetic/toxicodynamic, and population). Using a strong stakeholder co-development approach, these models will be combined in a One System framework taking a systems view on risk assessment and policy evaluation, including an international monitoring program.The One System framework is based on EFSA’s system ERA view, expanding on the tools used for bees to include butterflies, moths and hoverflies. The consortium partners are experts in the field needed for this development and are well-placed to facilitate the uptake of tools by European bodies to guarantee the project's future impact.Expected impacts target Destination impacts of better understanding and addressing drivers of biodiversity decline, interconnected biodiversity research using digital technologies, and understanding the biodiversity and health nexus at the ecosystem level.

Abstract Considering the frequency and severity of olfactory disorders associated with SARS-CoV-2 infection, attention to the olfactory loss has expanded. The aim of our study was to assess of smell disturbances 6 months after COVID-19. The study population consisted of 2 groups: 196 Post-COVID-19 patients who were hospitalized because of COVID-19, control sample–130 patients without reported smell disorders from general population-Bialystok PLUS study. People from both groups were asked to participate in the Sniffin Sticks Test (half year after the disease). Sniffin Sticks Test consisted of 12 standardized smell samples. The participant's test score was counted based on correct scent recognition. Middle/older age was related with lower likelihood of olfaction recovery. The biggest differences in recognition of particular fragrances were observed for: orange and lemon, lemon and coffee (p.adj

INTRODUCTION: Spinal cord stimulation (SCS) has emerged as a prevalent therapy for chronic neuropathic pain and failed back surgery syndrome (FBSS) over the past three decades, offering various stimulation types differentiated primarily by frequency. CASE REPORT: A 51-year-old male patient in 2016 underwent lumbar discectomy – L4/L5 due to symptomatic discopathy, which resulted in pain relief; however, the symptoms returned. In 2021 a Stimwave high-frequency (HF) SCS was placed epidurally at Th8–Th10. The patient reported substantial improvement after stimulation, nevertheless, after two weeks there was sudden exacerbation of his symptoms, especially in the lumbar region. Despite multiple attempts at program change and confirmation of the electrode location, there was no improvement. The HF stimulator was not removed owing to the risk of complications and 20% relief of pain in the right lower limb. After two years he was qualified for the implantation of newer generation of stimulators – BurstDR™ stimulation. An epidural electrode was implanted at Th8–Th10, followed by the placement of a BurstDR™ pulse generator. Currently, the patient has two active electrodes, one with HF stimulation, the other with BurstDR™ stimulation. CONCLUSIONS: Our case report demonstrates that there is no need to abandon SCS after the first failed attempt and it is worth trying stimulation with a different modulation. Furthermore, according to our center’s experience, the therapeutic effects of HF stimulation are quickly depleted and only after using burst stimulation was the expected result achieved. The reasons for this phenomenon are unknown and should be further researched.

Mapping the eco-evolutionary factors shaping the development of animals' behavioural phenotypes remains a great challenge. Recent advances in 'big behavioural data' research-the high-resolution tracking of individuals and the harnessing of that data with powerful analytical tools-have vastly improved our ability to measure and model developing behavioural phenotypes. Applied to the study of behavioural ontogeny, the unfolding of whole behavioural repertoires can be mapped in unprecedented detail with relative ease. This overcomes long-standing experimental bottlenecks and heralds a surge of studies that more finely define and explore behavioural-experiential trajectories across development. In this review, we first provide a brief guide to state-of-the-art approaches that allow the collection and analysis of high-resolution behavioural data across development. We then outline how such approaches can be used to address key issues regarding the ecological and evolutionary factors shaping behavioural development: developmental feedbacks between behaviour and underlying states, early life effects and behavioural transitions, and information integration across development.

Introduction: Antinuclear antibodies (ANA) are the hallmark of many connective tissue disorders (including lupus), which comprise roughly 5% to 10% of chronic debilitating diseases causing morbidity and mortality. In society, fear of these diseases increases illness-related uncertainty because the prognosis of progression is often difficult to determine and at least some symptoms fluctuate unpredictably. In the anti-vaccination movement, the question of the possible connection between vaccination and connective tissue disorders and other autoimmune diseases has grown to rank as an important argument for rejecting vaccination. In 2021, every fifth Polish first-degree nursing student decided to not be vaccinated against COVID-19. Objective: This study aimed to explore the prevalence of antinuclear antibodies in students vaccinated and unvaccinated against COVID-19. Participants and Methods: A single university cross-sectional study was performed in a small academic centre in Poland, where 210 students were recruited in 2022. All the participants were screened for SARS-CoV-2 IgG and antinuclear antibodies. Results: The mean age of the students who rejected vaccination was higher than that of those who were vaccinated. Among nursing students, 30.0% of vaccinated and 58.3% of unvaccinated individuals had COVID-19. The frequency of antinuclear antibodies was 3 times lower in vaccinated students than in unvaccinated students (2/159 vs 2/51; P > .05). Conclusion: The results of our study did not confirm the rationality of rejecting vaccinations against COVID-19 for fear of developing autoimmune diseases among healthy students.

Remnant vascular grafts may result in significant neurological deficits owing to compression of adjacent neural structures. We report this finding in two cases after extracorporeal membrane oxygenation decannulation and removal of an arteriovenous fistula in the upper extremity. In both cases, removal of the graft, patch arteriotomy, and external neurolysis resulted in significant recovery of neurological function. We review the preoperative workup, diagnostic studies, and technical approach to treatment in an effort to increase recognition among vascular and cardiovascular surgeons and to demonstrate a safe and effective management option through a multidisciplinary approach.

Pseudoaneurysm (PSA) is a rare complication of pancreatic transplantation and can present with gastrointestinal (GI) bleeding.We present a case of a 61-year-old male, who had a history of a pancreas transplant for type I diabetes mellitus 12 years ago, who presented with GI bleeding. He had a CT scan that showed a small PSA in the distal aorta near the arterial anastomosis of his previous pancreas transplant. He underwent an angiogram showing a distal aortic PSA with a wide sac. The patient was initially treated with observation and had recurrent bleeding. The patient had a repeat CT scan showing an increase in the size of the aortic pseudoaneurysm with contrast into the GI tract. He underwent an emergent endovascular stent placement with good recovery.Pancreatic transplantations have a low incidence of PSA; however, patients can present with sentinel gastrointestinal bleeding followed by more massive bleeding. These patients should undergo a CT scan with contrast and angiogram for accurate diagnosis and treatment.

Predation threat is a major driver of behavior in many prey species. Animals can recognize their relative risk of predation based on cues in the environment, including visual and/or chemical cues released by a predator or from its prey. When threat of predation is high, prey often respond by altering their behavior to reduce their probability of detection and/or capture. Here, we test how a clonal fish, the Amazon molly (Poecilia formosa), behaviorally responds to predation cues. We measured aggressive and social behaviors both under ‘risk’, where chemical cues from predatory fish and injured conspecifics were present, and control contexts (no risk cues present). We predicted that mollies would exhibit reduced aggression towards a simulated intruder and increased sociability under risk contexts as aggression might increase their visibility to a predator and shoaling should decrease their chance of capture through the dilution effect. As predicted, we found that Amazon mollies spent more time with a conspecific when risk cues were present, however they did not reduce their aggression. This highlights the general result of the ‘safety in numbers’ behavioral response that many small shoaling species exhibit, including these clonal fish, which suggests that mollies may view this response as a more effective anti-predator response compared to limiting their detectability by reducing aggressive conspecific interactions.

Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of tubular epithelial cells (TECs) were pre-treated with ATX-304 (20 µM, 4 h) prior to exposure to cisplatin (20 µM, 23 h). ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation. It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot for neutrophil gelatinase-associated lipocalin (NGAL) (control 3.3 + 1.8-fold vs ATX-304 1.2 + 0.55-fold, P = 0.002), and histological injury (control 3.5 + 0.59 vs ATX-304 2.7 + 0.74, P = 0.03). In TECs, pre-treatment with ATX-304 protected against cisplatin-mediated injury, as measured by lactate dehydrogenase release, MTS cell viability, and cleaved caspase 3 expression. ATX-304 protection against cisplatin was lost in AMPK-null murine embryonic fibroblasts. Metabolomic analysis in TECs revealed that ATX-304 (20 µM, 4 h) altered 66/126 metabolites, including fatty acids, tricarboxylic acid cycle metabolites, and amino acids. Metabolic studies of live cells using the XFe96 Seahorse analyzer revealed that ATX-304 increased the basal TEC oxygen consumption rate by 38%, whereas maximal respiration was unchanged. Thus, ATX-304 protects against cisplatin-mediated kidney injury via AMPK-dependent metabolic reprogramming, revealing a promising therapeutic strategy for AKI.

Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.