A network intrusion detection model based on the hybrid deep learning algorithm of TCN-CNN is designed to improve the success rate of network intrusion detection. The model integrates the temporal convolutional neural network (TCN) and convolutional neural network (CNN) frameworks to enhance the accuracy of network intrusion detection. First, TCN is used to extract high-frequency behavior features from long-time sequence data, forming a feature matrix by concatenating multiple feature vectors and converting it into an image for CNN convolutional learning. The optimal weight of the hidden layer feature matrix is then obtained, and the powerful image recognition ability of CNN is used to perform category mapping to assist the network intrusion detection system in achieving network anomaly detection. The experimental results show that the model can detect 94.56% of the five different DDoS attacks, which has a higher accuracy and faster convergence rate than other machine learning-based intrusion detection models.

Methotrexate and Cyclosporin Improve Skin Biomarkers in Paediatric Atopic Dermatitis: Results from the TREAT TrialTo the Editor,Methotrexate (MTX) and cyclosporin (CyA) are the main conventional systemic treatments for severe atopic dermatitis (AD) globally.1,2 The complex interaction of cutaneous immune biomarkers and their modulation during therapy with these drugs is poorly understood.3 In the Treatment of severe Atopic Eczema in children Trial (TREAT) CyA led to faster disease control, while MTX showed sustained disease control post-therapy.4 Here we explore skin immune biomarkers in TREAT participants randomised to either CyA (4mg/kg/day) or MTX (0.4mg per week) for 36 weeks with 24 weeks follow-up after therapy cessation.4 43 participants were included (22 CyA; 21MTX). Tapestrips were taken from the volar forearm at baseline, 12, 36 and 60 weeks. Concentrations of NMF and immune biomarkers were measured. Please see supplementary materials for sampling, laboratory and statistical methods.Baseline demographics were well balanced across study groups, including disease severity, measured by Eczema Area and Severity Index (EASI; Table S1). Changes in EASI scores at the biomarker sampling time points reflect the disease severity changes in the full TREAT trial population (Fig. S1).MTX and CyA drove significant changes in stratum corneum cytokine levels. While there were no statistically significant biomarker differences between the treatment groups, it is noteworthy that the number of biomarkers showing significant change from baseline was higher with MTX than for CyA (Fig. 1, Table S2). Innate cytokines, CXCL8 and IL-18 were altered with both treatments. CXCL8 decreased from baseline at 12 weeks with MTX and CyA, at 36 weeks with MTX only and at 60 weeks with both drugs. IL-18 decreased at 12 weeks with CyA, at 36 weeks with both drugs and at 60 weeks with MTX only. The innate cytokine IL-1α increased at all timepoints compared to baseline only with MTX. Similarly, the skin barrier biomarker NMF increased at weeks 12 and 36 only with MTX. Th2 cytokines decreased with both treatments: CCL17 at 12 and 36 weeks with MTX only and at 60 weeks with both treatments, while CCL27 decreased at 12 weeks with CyA only, at week 36 with both drugs and at 60 weeks with MTX only. IL-17 decreased with both drugs at week 36 and the Th1 biomarker CXCL10 decreased at week 60 with CyA only. All biomarkers except NMF and IL-1α positively correlated with EASI score (Fig. 2). CXCL8/TARC showed the strongest correlation (r=0.50; P<0.0001).Systemic treatment with both MTX and CyA led to clinical improvement with differential cytokine signatures, indicating that MTX and CyA not only suppress inflammation, but also normalize immune responses mediated by cytokines involved in innate (IL-1α, IL-18, CXCL8), Th1 (CXCL10), Th17 (IL-17A) and Th2 (CCL17 and CCL27) immunity. Significant changes from baseline were found for the skin barrier biomarker NMF, but only with MTX.Normalization of NMF levels can also be attributed to a decrease in Th2 cytokines, which inversely regulate filaggrin gene expression. CCL17 and CCL27, Th2 mediators in AD, normalized to a larger extent after MTX compared to CyA, suggesting MTX may modulate Th-2 suppression pathways and normalize skin barrier function. The strong correlation of CXCL8 and CCL27 with EASI score is consistent with previous stratum corneum biomarker studies.5-6In conclusion, MTX and CyA improve clinical outcomes in AD and modulate the cutaneous immune response. MTX has a more pronounced effect on certain immunological and skin barrier biomarkers compared to CyA, indicating potential differences in their mechanisms of action, and suggesting that MTX may offer additional benefits in the treatment of AD, even after treatment cessation.

This letter presents a low-distortion bootstrapped switch for improving sampling network linearity. The dynamically driven gate approach and the dynamically driven DNW (Deep N-well) technique are proposed to reduce the parasitic capacitance at crucial nodes. Simulated in a 180nm CMOS process, the proposed switch achieves a total harmonic distortion (THD) of -102.1dB at an 80MHz sampling frequency. This is an 21.4dB increase in THD, over the conventional switch.

Species-specific genomic information has the potential to transform modern conservation management strategies through improved genomic impact assessment and management outcomes. Gaining genomic insights into genetic diversity, adaptability, and potential resilience against infectious diseases is essential to enhance conservation efforts for threatened species. Here, we describe the development of a custom 50K SNP array for Pseudophryne corroboree, a critically endangered amphibian threatened by the amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and illustrate its application in characterising the species’ genomic architecture. The array comprises 48,386 SNPs, with an average density of 5.45 SNPs per Mb and was effective in genotyping multiple tissue types, including non-lethal buccal swabs. Of the SNPs, 82.1% were polymorphic across 910 captive-bred P. corroboree individuals derived from 54 families. Our analysis of this population revealed evidence of ancestral inbreeding, the presence of two historic bottlenecks occurring approximately 100 and 10 generations ago, with the latter coinciding with the arrival of Bd to Australia. We also demonstrate the array’s cross-species amplification potential, successfully converting 21,077 (43.6%) polymorphic loci across three closely related anurans. This array is a valuable resource for future investigations aimed at understanding the genetic basis of disease resistance and developing management strategies for improving reintroduction outcomes in P. corroboree.

Aim: Genetic susceptibility has been identified in idiosyncratic drug-induced liver injury, a potentially severe adverse reaction towards drugs, herbal products and dietary supplements. Drug-induced liver injury epigenetic signatures could help explain genetic regulatory mechanisms behind this disease and might provide disease biomarkers. This systematic review aims to analyse all available information on epigenetic risk association studies, as well as to include additional information on receiver operating characteristic analyses in idiosyncratic drug-induced liver injury when present. Methods: The main inclusion criteria were population studies on idiosyncratic drug-induced liver injury with significant risk association between drug-induced liver injury and an epigenetic regulation mechanism. Results: Out of the seven included articles six were focused on DNA methylation and one on long non-coding RNA. All of the studies were on drug-induced liver injury due to anti-tuberculosis drugs and came from Asia. CpG site methylation in the CYP2D6 (Odds ratio:9.19, 95% confidence interval:3.62-25.89, p-value:0.001) and NAT2 (Odds ratio:8.37, 95% confidence interval:2.39-29.32, p-value:0.001) promoters conferred the highest risk. Regarding the potential of epigenetic signatures as biomarkers, LINE-1 and ALU transposable elements hypomethylation levels showed an area under the curve value of 0.94, indicating their potential as biomarkers. Conclusions: The majority of the studies were on DNA methylation and hepatotoxicity due to anti-tuberculosis drugs, with all of them coming from Asia where tuberculosis is a public health burden. While this is an area that requires further research, the results of this systematic analysis suggest the potential of epigenetic regulation as a new diagnostic and therapeutic target.

Background: Pediatric patients with progressive and refractory solid tumors face a challenging prognosis. Despite advancements in treatments like immunotherapy and targeted therapy, survival rates remain low for certain tumor types. Decision-making in these complex cases often necessitates a multidisciplinary approach, integrating risk-based management, precision medicine, and access to clinical trials. Artificial intelligence (AI) technologies, particularly large language models (LLMs), hold promise for improving clinical reasoning and decision support in pediatric oncology. Procedure: This study evaluated the decision-making capabilities of five AI tools—ChatGPT, Gemini, Claude, Perplexity, and OpenEvidence—in six hypothetical cases of refractory or progressive pediatric solid tumors. Each AI tool was presented with two sequential queries: a request to generate potential treatment options and then a request to identify and justify the most appropriate option from its initial list. Results: The AI tools generated a total of 124 treatment recommendations, with an average of 24.8 per tool. Clinical trial enrollment was the most frequently selected ”best option,” accounting for 55.2% of cases. Other notable recommendations included targeted therapy (17.2%), surgery (10.3%), chemotherapy (10.3%), best supportive care (10.3%), and immunotherapy (3.4%). Notably, the AI tools exhibited distinct tendencies in their decision-making approaches, with some favoring aggressive interventions, and others emphasizing supportive or palliative care. Conclusions: AI tools demonstrate potential for assisting with complex treatment decisions in pediatric oncology, particularly by identifying clinical trial options. However, the observed variability in recommendations underscores the need for careful human oversight to ensure that AI-generated suggestions align with clinical evidence, patient and family preferences, and the overall goals of care. Future research should explore how AI tools can be further refined to incorporate nuanced patient-specific information and address the emotional and psychological impact of AI-assisted decision-making.

Background: Spiritual care is recognized as an essential component of standard care for children with cancer and their families. Oncologists lack training in navigating spirituality discussions in primary cancer care. The current landscape of spiritual dialogue during clinical oncology encounters remains understudied. Procedures: This qualitative study aimed to describe the frequency, context, and content of religious and spiritual communication between pediatric neuro-oncologists, caregivers, and patients with brain tumors during disease reevaluation encounters. This study is part of the U-CHAT trial (NCT02846038), a prospective longitudinal investigation of realtime clinical communication across the trajectory of poor prognosis cancer. Patients with brain tumors and their caregivers were eligible if their primary oncologist estimated survival ≤ 50%. All disease reevaluation encounters for enrolled patients were audiorecorded and underwent rapid qualitative analysis to identify, summarize, and synthesize religious and spiritual communication. Results: Religious or spiritual references were identified in 23 (18%) of 129 total encounters. References usually comprised a single religious or spiritual term, with “prayer”-related language representing the majority of references. Caregivers introduced spirituality dialogue more often than oncologists (65% vs 35%). References were most often identified in the context of discussion about an uncertain or uncontrollable future. Conclusions: Results suggest oncologists rarely integrate spiritual care into disease reevaluation discussions. In light of recommendations from multiple consensus groups to integrate spiritual care into cancer care, future work should explore how generalist spiritual care training could better equip oncologists to attend to spiritual needs that arise along the cancer trajectory.

As wind energy development expands across the Great Plains, there is potential to adversely affect species that require undisturbed tracts of native grasslands, such as the lesser prairie-chicken (Tympanuchus pallidicinctus; LEPC). Effects of wind development on LEPC movement and demographic rates have been minimal when turbines are sited in cultivated cropland and grassland habitats are available nearby, but there are gaps in the overall understanding of how LEPC populations will respond to wind energy development over the long term. Reducing these knowledge gaps and improving our decision-making process is key to balancing the needs of the wind energy industry and conservation of the species. We evaluated trends in LEPC lek attendance and persistence following construction of the Cimarron Bend Wind Resource Area (CBWRA) in southern Kansas, USA from 2017-2024. We used Bayesian generalized linear regression models to evaluate lek stability and the probability of blinking out with various environmental and anthropogenic covariates. We modeled total lek attendance with years since facility construction as a predictor. Of the 37 leks included in analysis, we found leks located in areas with higher turbine counts and had lower median attendance during active years were less stable, and leks with higher grass cover were less likely to blink out over our 8 years of monitoring. However, these effects did not seem to impact the local LEPC population at CBWRA, given that the total lek attendance had a positive trend across the 8-year study, providing additional support that siting turbines in cultivated croplands and conserving large intact tracts of grasslands appear to be important minimization measures for LEPC. Regardless, it remains to be seen how LEPC would be impacted by wind energy development in intact grassland-dominated landscapes (i.e., core habitat).

The spatial configuration and management of agricultural and other land-use practices can affect ecological assemblages, but how resident and migratory species respond to land uses is not well known, hindering our understanding of the effects of land use on biodiversity. Here, we compare alpha and beta diversity and ecosystem functioning for resident and migratory birds across three land uses: (1) primary forest, (2) secondary forest, and (3) cattle pasture. Compositionally, resident bird assemblages exhibited gradual shifts across habitats with diversity steadily declining with increasing distance from a protected area and reductions in understory vegetation. In contrast, migratory bird community composition clustered into five distinct groups, shifting 50-60% less than resident assemblages across the same gradients with no declines in richness. We found that migratory bird abundance was greater in secondary forest and cattle pasture, and migratory insectivores compensated for 68% of the abundance losses of resident forest insectivores in secondary forests and cattle pastures. Among the insectivores, increases of migratory birds in secondary forest and cattle pasture compensated for the abundance declines of resident birds that utilize foliage gleaning and sallying foraging methods. Our findings underscore the importance of local landscape evaluation and management around protected areas, highlighting the unique responses of resident and migratory birds to land use and the potential mechanisms sustaining ecosystem functions in modified habitats.

Objectives Superficial parotidectomy is a common surgery performed by Otolaryngologists. Elderly patients may be undertreated due to perceived complications. Our study aimed to evaluate the differences in early postoperative outcomes in patients over age 75. Methods The National Surgical Quality Improvement (NSQIP) database identified patients undergoing superficial parotidectomy. Cohorts were created for patients younger and older than 75. Bivariate and multivariate analyses compared rates of postoperative complications, reoperation, length of stay and readmission. Subgroup analyses were conducted for benign and malignant disease. Results Our query identified 2472 patients, including 309 elderly and 2163 younger patients. Bivariate analysis showed significantly higher rates of stroke (p = 0.043), readmission (p < 0.001), hospital stay longer than two days (p < 0.001) and need for transfusion (p = 0.026) in elderly patients. On multivariate analsysis, readmission rates (OR: 2.648, 95% CI: 1.035-6.775, p = 0.042) and increased length of stay (OR: 2.405, 95% CI: 1.348-4.298, p = 0.003) were significantly worse in elderly patients. Subgroup analysis showed that elderly patients treated for malignant parotid tumors were more likely to be readmitted (OR: 6.928, 95% CI: 1.293-37.111, p = 0.024). Conclusion Superficial parotidectomy appears to be a safe when performed in elderly patients. Main risks to consider in this population include readmission and increased hospital length of stay. Major postoperative morbidities were not identified on multivariate analysis.

Prominent ears affect 5% of the population(1). For those who wish to undergo corrective surgery, pinnaplasty reduces pinna prominence. This has proven improvement on quality of life (QOL) for patients. Pinnaplasty carries risk, which may lead to delay in this improvement of QOL, if for example a complication leads to infection, or require surgical revision The use of Mustardé sutures for pinnaplasties, first described in 1963 is a well established surgical approach to treat protruding ears. This approach has good outcomes, however can lead to suture-extrusion. Here we explore the use of Biodesign surgical mesh to cover the Mustardé sutures to prevent suture extrusion, and reduce the likelihood of the need for revision surgery.

Hyperspectral technology has received great attention for estimating aboveground plant biomass. Corrections using ground spectrometer data have been proposed for more accurate integrated assessments of aboveground plant biomass. In this study, we sampled the aboveground plant biomass and the corresponding hyperspectral data from three types of alpine grassland ecosystems (alpine desert, alpine steppe, and alpine meadow) from the Qinghai-Tibetan Plateau to improve the biomass estimation accuracy. We used partial least squares regression and the vegetation indices (VIs) (using all two-band combinations (601*601combinations in all) involving 601 narrow bands between 400nm and 1000nm), and the optimal band combinations were used to calculate four most commonly used VIs. We found that the VIs are better than the least square method for alpine meadow, and that the most effective combinations were shown in the combinations of reflectance at the red edge (rather than red) and near-infrared bands(728nm,764nm). For alpine steppe and alpine desert, however, partial least squares regression is better than VIs. While the most important band for alpine steppe is between 600nm and 700nm in the red spectrum, the most important band for alpine desert is around 400nm. Our results can provide a theoretical basis for accurately estimating the aboveground plant biomass of different grassland types in the Qinghai Tibet Plateau.

Removal of host cell proteins (HCPs) during biotherapeutics manufacturing is vital for ensuring patient safety and biotherapeutic stability and supply. Yet, this goal remains exceptionally challenging for some HCPs. For example, phospholipase B-like 2 (PLBL2) from Chinese hamster ovary (CHO) cells (the workhorse for therapeutic protein production) plagues engineers by evading typical purification strategies. New tools have emerged to aid HCP removal, but technologies directed at specific HCP species are still nascent, and an urgent, unmet need remains. Herein, we present a platform approach for the targeted removal of specific, challenging HCPs – even those present at sub-ppm levels. Using CHO PLBL2 as a model, we site-specifically modify and immobilize polyclonal antibodies directed against CHO PLBL2, which exists as multiple proteoforms (e.g., size and charge variants). The immobilized antibodies retain their antigen binding, enabling capture and clearance of CHO PLBL2 from an array of bioprocess streams, including IgG4 and IgG1 antibodies. Although centered on CHO PLBL2, our approach should be broadly applicable to numerous other HCPs across the increasingly diverse biotherapeutic landscape. Additionally, CHO PLBL2 recovered from the polyclonal antibodies exhibits multiple molecular size variants, opening the door to further characterization to identify other proteoforms. This insight can, in turn, guide purification development, even in processes without custom affinity anti-HCP steps.

The concept of damage-associated molecular patterns (DAMPs), derived from Polly Matzinger’s danger hypothesis in 1994, provides a theoretical framework for understanding immune system recognition and response to cellular distress in the absence of pathogens. DAMPs, released by stressed, dying, or dead cells, serve as host signals that initiate, sustain, and amplify inflammatory responses. These molecular patterns are essential in mediating the interaction between innate and adaptive immunity, elucidating the mechanisms behind immune cell recruitment and activation across a range of pathological states. This review systematically explores the evolution of the DAMP hypothesis, detailing the classification, biogenesis, and cellular origins of DAMPs, along with their associated signaling pathways and release mechanisms. Furthermore, it discusses the clinical implications of DAMPs and examines their therapeutic potential in various pathological conditions, underscoring their increasing significance in medical research and therapeutic innovation.

Macrophages are one of the important cell types of the immune system, demonstrating significant adaptability that enables them to transform to different phenotypes in response to their surrounding environment. This review examines the characteristics of different macrophages phenotypes that can produce both pro-inflammatory and anti-inflammatory cytokines. The M1 phenotype, known for its inflammatory features, plays a pivotal role in fighting infections and tumors; however, it may also lead to tissue injury and persistent inflammation and play a role in autoimmune and inflammatory diseases. In contrast, the M2 phenotype is linked to anti-inflammatory activities and the processes of tissue repair. Recent progress in the characterization of unique macrophage phenotypes has opened up novel therapeutic approaches for the treatment of chronic inflammatory conditions, autoimmune disorders, and cancer diseases. This review highlights the critical role of macrophage polarization, illustrating how different stimuli can change macrophages fate and change their responses. Additionally, it explores the consequences of macrophage plasticity on the advancement of diseases and the effectiveness of treatments. This article seeks to clarify the processes involved in macrophage polarization and the resulting functional implications, with the goal of offering insights into therapeutic approaches that leverage the adaptability of macrophages to improve immune responses or alleviate disease states. Furthermore, it introduces all the phenotypes that discovered until to date. A comprehensive understanding of these dynamics cells is crucial for the advancement of targeted immunotherapies, which have the potential to develop treatment strategies for various medical conditions.

In the realm of myocardial ischemia/reperfusion (I/R) injury, the intricate interplay between RNA modifications and cellular responses remains a subject of intense investigation. Here, we elucidate a pivotal role of ALKBH5-mediated RNA N6-methyladenosine (m6A) demethylation in safeguarding against myocardial I/R-induced injury through the inhibition of ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation. Our study unveils a novel mechanism wherein ALKBH5, a member of the AlkB family of dioxygenases, acts as a critical regulator of RNA m6A modification, thereby influencing the susceptibility of cardiomyocytes to I/R injury. Using a combination of in vitro and in vivo models, we demonstrate that ALKBH5 expression is dynamically modulated in response to myocardial I/R insult. Mechanistically, ALKBH5-mediated demethylation of specific RNA transcripts, orchestrated by its catalytic activity, mitigates ferroptosis by regulating the expression of key ferroptosis-related genes. Importantly, we identify ferroptosis-suppressor-protein 1 (FSP1) as a downstream effector of ALKBH5-mediated m6A demethylation, linking the protective effects of ALKBH5 to the inhibition of ferroptosis in cardiomyocytes. Furthermore, our findings highlight the clinical relevance of ALKBH5 in myocardial I/R injury, as evidenced by the exacerbation of cardiac dysfunction and infarct size in ALKBH5-deficient mice subjected to I/R insult. Conversely, overexpression of ALKBH5 confers robust protection against myocardial I/R injury, underscoring its therapeutic potential in the management of ischemic heart disease. Collectively, our study delineates a novel axis involving ALKBH5-mediated RNA m6A demethylation and FSP1-dependent inhibition of ferroptosis as a critical mechanism for cardio protection against myocardial I/R-induced injury. Targeting this axis holds promise for the development of innovative therapeutic strategies aimed at attenuating myocardial I/R injury and improving clinical outcomes in patients with ischemic heart disease.

Effect of sand-fixing shrubs on water redistribution is a key link in the water cycle in sandy areas. However, previous studies have not sufficiently focused on the coupling analysis of the aboveground morphology of these shrubs with throughfall (TF) and soil evaporation (SE), limiting the accurate assessment of their water-holding effect. This study focused on three sand-fixing shrubs, Salix psammophila, Artemisia ordosica, and Caragana korshinskii, along the eastern edge of the Hobq Desert, investigating TF and SE changes under varying rainfall conditions and across different spatial environments. The water-holding index (W) of these shrubs was analyzed in response to rainfall and its correlation with the aboveground morphological traits. Results indicate that under 5.8 mm rainfall conditions, the W values for S. psammophila and C. korshinskii ranged between –0.1 and 0.0 while those for A. ordosica ranged from 0.03 to 0.08. During heavy rainfall (> 10.7 mm), the W values for all shrubs increased to between 0.00 and 0.17, illustrating the enhanced water-holding effect of shrubs under such conditions. Shrub configuration factors, such as the ratio of the branch diameter (RBD), overall branching rate (OBR), and branch ground angle, were well-fitted to W. RBD and OBR were the main factors influencing the water-holding effect of sand-fixing shrubs, explaining 77.3% of the variation in W for sand-fixing shrubs. This study highlights the pivotal role of shrub morphology in regional water cycles, revealing that shrubs with a higher OBR and RBD and smaller branch-to-ground angle exhibit a superior water-holding effect.

Apurinic/apyrimidinic endonuclease 1 (APE1) is a critical enzyme in the base excision repair (BER) pathway, essential for preserving cellular equilibrium. Variations in APE1 activity within blood or tissues can provide significant insights for clinical cancer screening and disease diagnosis. Consequently, the detection of APE1 activity is critical for clinical diagnostics. However, there is currently a deficiency in rapid, straightforward, and sensitive methods for APE1 detection. To address this issue, we developed a method that integrates nicking enzyme assisted amplification (NEAA) with CRISPR-Cas12a signal amplification, enabling one-pot detection of APE1 activity. This method utilizes NEAA to produce a substantial quantity of target DNA that is complementary to the crRNA, thereby triggering the trans-cleavage activity of Cas12a. The activated Cas12a then amplifies and emits signals by cleaving the Reporter probe. Our strategy allows for the swift and precise detection of APE1, with a detection threshold of 1×10 -6 U/mL and a linear detection range of 5×10 -6 to 0.1 U/mL. It has been effectively utilized for the detection of APE1 in biological samples.

Comprehensive Summary Compared with traditional fluorescent materials with aggregation-caused quenching (ACQ) effect, small organic molecules with aggregation-induced emission (AIE) characteristics show advantages in the field of biomedical detection due to their special structure and optical properties. However, the single function of fluorescent materials can no longer meet the needs of multiple applications. Preparation of multifunctional materials will become a new research craze. In this paper, a D-π-A organic small molecule ( E)-9-Butyl-3-(2-(pyridin-4-yl)vinyl)-9 H-carbazole ( PC) was designed and synthesized by Wittig reaction with modified carbazole group as electron donor (D) and pyridine as electron acceptor (A). The results of X-ray single crystal diffraction, spectral measurement and theoretical calculation show that PC exhibits good aggregation-induced emission properties due to the stacking model of J-aggregation. In addition, we found that PC displays acid-stimulated fluorescence response properties, expanding the application fields of PC in encrypted information transmission, fluorescent ink, and cell imaging, injecting new vitality into multifunctional materials.

Identifying genomic regions under selection is crucial for comprehending the evolutionary history of the domestic chicken. The Arabian Peninsula (AP) indigenous chickens are mostly found outdoors, being reared alongside other livestock for production purposes. These birds show high resilience to extreme temperatures (hot and cold), typical of the desert environment. The selection pressures responsible for unique local adaptations in these birds remain largely unidentified. Here, we aimed to investigate the genome diversity and structure of fifteen indigenous chicken populations including thirteen populations from the AP (n = 5), Ethiopia (n = 6), and the Republic Popular of China (n = 2). We also included two commercial chicken populations, Fayoumi (selected for heat tolerance) and Chantecler (known for its cold tolerance). The PCA separated all the populations based on their geographic areas of origin. PC1 separates the Ethiopian populations from the Chinese and AP populations. PC2 separates the AP populations from the Chantecler, and the Ethiopian populations from the Dulong (China) and Chantecler. The genome-wide signatures of analyses identified many candidate regions under positive selection. They include genes which may be associated with thermotolerance. These are involved in energy balance and metabolism ( SUGCT, HECW1, MMADHC), cells apoptosis ( APP, SRBD1, NTN1,  PUF60, SLC26A8, DAP, SUGCT), angiogenesis ( RYR2, LDB2, SOX5), skin protection to solar radiation ( FZD10, BCO2,  WNT5B, COL6A2 and  SIRT1) as well as growth ( NELL1). Our findings suggest that Arabian chicken populations have a distinct gene pool polymorphism in relation to their adaptation to the harsh climatic environments of the Arabian Peninsula.

Conjugate gradient methods are important first-order optimization algorithms both in Euclidean spaces and on Riemannian manifolds. However, while various types of Riemannian conjugate gradient methods have been studied, the iteration complexity analysis remains unknown. This paper proposes a novel Riemannian conjugate gradient method for nonconvex problems with an iteration complexity guarantee. In particular, we introduce a novel restart condition, leading to a function decrease at each iteration. Our method converges to an ϵ-stationary point with an iteration complexity of O ( ϵ − 2 ) . To the best of our knowledge, this is the first Riemannian conjugate gradient method with iteration complexity guarantees. Numerical experiments on Rayleigh-quotient and Brockett-cost-function minimization problems demonstrate the efficiency and practical applicability of the proposed method.

Background: Trauma exposure is pervasive in people with an At Risk Mental State (ARMS) and is associated with adverse clinical and functional outcomes. While promising developments have been made in treating trauma in psychosis, evidence regarding the efficacy of trauma therapies in ARMS individuals is limited. This trial aims to evaluate the feasibility of conducting a future randomised controlled trial (RCT) to determine the efficacy of Eye Movement Desensitisation and Reprocessing (EMDR) and Trauma Focused Cognitive Behavioural Therapy (TF-CBT) in people with ARMS. Method: 75 ARMS individuals with a history of trauma will be randomised to receive 24 sessions of EMDR plus treatment as usual (TAU), 24 sessions of TF-CBT+TAU, or TAU alone. Feasibility will be determined against pre-specified thresholds for recruitment, retention, treatment engagement, and fidelity. To examine the promise of efficacy of EMDR and TF-CBT, participants will complete a battery of clinical and mechanistic measures at baseline and 9-month post-randomisation, including assessments of attenuated psychotic symptoms and post-traumatic symptoms. Clinical notes will be reviewed to identify transitions to first episode psychosis up to 12-months post-randomisation. Qualitative interviews with trial participants, therapists, and professional stakeholders will explore the acceptability of EMDR and TF-CBT and factors to facilitate future implementation of trauma therapies in routine practice.  Conclusions: If a large-scale RCT is deemed feasible, it will be possible to establish whether EMDR and/or TF-CBT represent beneficial treatments to augment existing evidence-based care for individuals at ultra-high risk for future psychosis, potentially reducing transition rates and improving clinical outcomes for ARMS individuals.

Objective: This study aimed to investigate the relationship between dopamine receptor D2 (DRD2) and catechol-o-methyltransferase (COMT) gene polymorphism, hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes functions, and macroprolactinemia induced by antipsychotics. Methods: A total of 133 patients with schizophrenia were selected and given risperidone (4～6mg/d) monotherapy. The polymorphisms of DRD2 Taq1A and COMT Val158Met were analyzed using RFLP-PCR at baseline, and the levels of total prolactin (T-PRL), macroprolactin, C peptide (C-P), estradiol (E2), cholesterol (TC), low density lipoprotein (LDL), insulin, cortisol, thyroid function, and reproductive hormone were measured at baseline and the end of the fourth week of treatment. The patients were divided into a hyperprolactinemia group and a macroprolactinemia group according to their levels of T-PRL and macroprolactin, and the differences in the above indexes between the two groups were analyzed. Results: There was no significant difference in the DRD2 Taq1A or COMT Val158Met gene polymorphisms between the two groups. However, after four weeks of treatment, significant differences were observed between the two groups in terms of C-P ( t= 2.16, p=0.04), E2 ( t=-3.89, p<0.001), TC ( t= -2.54, p=0.01), insulin ( t=-3.93, p<0.001), T3 ( t= 2.31, p= 0.02), and FT3( t=2.05， p=0.04). Conclusion: DRD2 Taq1A and COMT Val158Met gene polymorphisms may not be effective in predicting macroprolactinemia, but changes in C-P, E2, TC, insulin, T3 and FT3 levels may have some suggestive significance for the differentiation of hyperprolactinemia and macroprolactinemia.

A document by Ahmed Abdullah. Click on the document to view its contents.