Adoptive regulatory T cell (Treg) trasfer represents a potential therapeutic option to control immune responses in organ transplantation, graft vs host disease, and autoimmunity, including type 1 diabetes. Treg for adoptive therapy are traditionally sorted and expanded in vitro with high doses of IL-2, showing stability and suppressive capacity, but with some limitations in terms of long-term survival once infused in patients. Here, we tested a novel expansion protocol in which we added IL-7 (IL-7 method, IL-7M) to the traditional standard method (StM) using IL-2. We showed that naïve Treg express significant levels of CD127 and robustly respond to IL-7 by phosphorylating STAT-5. Naive Treg expanded with the IL-7M were highly enriched in CD45RA +CD62L +CD95 + showing a reduction in the final cell yield and suppressive function. Treg expanded with the IL-7M preserved telomere length and were more resistant to cytokine withdrawal and fas-mediated apoptosis. Overall our data indicate that it is possible to expand naïve Treg in the presence of IL-7 to generate a final Treg product enriched in poorly differentiated CD45RA + cells and with better resistance to stress and apoptosis, potentially improving the long-term survival of Treg in adoptive transfer protocols.

In this paper, Short-term predicting of load and spinning reserve is first performed using a combination of ANFIS and meta-heuristic algorithms including Differential Evolution (DE), Genetic Algorithm (GA) and Particle Swarm Optimization (PSO). The ANFIS-PSO combination is selected as the best ANFIS combination in load and spinning reserve prediction with a lower error criterion than other methods. As a DL method, LSTM network can provide good accuracy for load and spinning reserve forecasting. In the optimal ANFIS-PSO method, the average error value is low, but the error variance is high, on the contrary, in the LSTM method, the average error value is high, and the error variance is low. Therefore, we use the combination of ANFIS-PSO and LSTM to reduce the average error and error variance to an acceptable level. The weighted average method is as follows: the accuracy of each Method is obtained in the training step, then the predicted value for each data in the test step is calculated in each Method, then they are multiplied, and after that added together, finally will be divided to the total accuracy of two methods. The results obtained from the weighted average Method show the success of the proposed Method.

Randomized response technique (RRT) models are commonly used to estimate proportion of sensitive trait in survey sampling. In this study, we propose an improved class of estimators for sensitive trait when population level information is available on a non-sensitive auxiliary variable. This class of estimators is based on a generalization of the famous Kuk’s (1990) estimator and a difference estimator proposed by Diana and Perri (2009). We validate the results using survey data collected at the university of Wah, Pakistan. We also use a data set used earlier by Zaizai (2006).

This paper studies the Riemann boundary value problems on the Archimedean spiral. We characterized the functions which are intergrable on the Archimedean spiral. We also study the asymptotic behaviors of Cauchy-type integral and Cauchy principal value integral on Archimedean spiral at the origin and infinity. At the end, we discuss the Riemann boundary value problems for sectionally holomorphic functions with the Archimedean spiral as their jump curve and obtain the explicit form.

Objective This work explores the perceptions of obstetric clinicians about Artificial Intelligence (AI) in order to bridge the gap in uptake of AI between research and medical practice. Identifying potential areas where AI can contribute to clinical practice, enables AI research to align with the needs of clinicians and ultimately patients. Design Qualitative interview study. Setting A national study conducted in the Netherlands. Sample Dutch clinicians working in obstetrics with varying relevant work experience, gender, and age. Methods Thematic analysis of qualitative interview transcripts. Results Thirteen gynaecologists were interviewed about hypothetical scenarios of an implemented AI model. Thematic analysis identified two major themes: perceived usefulness and trust. Usefulness involved AI extending human brain capacity in complex pattern recognition and information processing, reducing contextual influence, and saving time. Trust required validation, explainability and successful personal experience. This result shows two paradoxes: firstly, AI is expected to provide added value by surpassing human capabilities, yet also a need to understand the parameters and their influence on predictions for trust and adoption was expressed. Secondly, participants recognised the value of incorporating numerous parameters into a model, but they also believed that certain contextual factors should only be considered by humans, as it would be undesirable for AI models to utilize that information. Conclusions Obstetricians’ opinions on the potential value of AI highlight the need for clinician-AI researcher collaboration. Trust can be built through conventional means like RCTs and guidelines. Holistic impact metrics, such as changes in workflow, not just clinical outcomes, should guide AI model development. Further research is needed for evaluating evolving AI systems beyond traditional validation methods.

Objective: To find out whether the prediction model using a machine learning approach can have comparable accuracy with the current state-of-the-art trisomy detection methods in extremely low-depth sequencing data. Verify the practical feasibility of being used for clinical auxiliary screening of fetal trisomy. Design: A public dataset with 144 samples is divided into training/validation/test (testA) set. A dataset with 270 sequencing samples was used for independent testing. Setting: Samples are from Hong Kong, China; London, England; Amsterdam, the Netherlands; and Beijing, China. Population: 414 maternal blood samples were analyzed for this study. Methods: The machine learning method for low-depth short sequencing data from maternal blood. Main Outcome Measures: Fetal karyotype was analyzed by interventional prenatal diagnosis or obtaining cord blood after birth. Results: We demonstrate the predictive ability of our method by testing on data from different sources. The final best model achieved an AUC of 99.85% in predicting T21 using chr21 features which are the DNA fragment concentrations. The AUC is 99.50%, and 97.70% in predicting T18 and T13 with all features from 24 chromosomes. PPV was 91.67%, 93.33%, and 83.33% in predicting T21, T18, and T13, respectively. The NPV to identify T21, T18, and T13 were 100%, 99.33%, and 98.70%, respectively. Our approach does not need to calculate fetal fraction (FF) and can handle samples from a wide range of gestational ages (GA), twin pregnancies and fetal mosaicism. We achieved high PPV with low-depth sequencing and robust performance in an independent dataset. Conclusion: Our approach can achieve comparable accuracy with the current best methods. Our pipeline can be an important aid for the detection of fetal trisomy in clinical NIPT.

Objective: To examine CGM feedback with the subsequent development of gestational diabetes (GDM), maternal glycaemic control, and glycaemic variability during pregnancy with randomisation 1:1 with one study arm receiving CGM feedback by intermittent scanning (unblinded group), versus masked feedback (blinded group). Design: Prospective, single-center, randomized controlled trial Setting: Single tertiary care hospital Population: Pregnant women recruited in the first trimester of pregnancy Methods: We assessed GDM and plasma glucose levels diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24-28 weeks as a primary outcome. The secondary outcome was CGM-derived parameters of glycaemic variability across the first (9-13 weeks), second (18-23 weeks), late second and early third (24-31 weeks) and third trimester (32-33weeks). Results: Over 47 months, 206 pregnant women were enrolled at 9-13 weeks. There were no significant differences with GDM outcomes, fasting, 1-hour or 2-hour plasma glucose concentrations between study arms. The unblinded group had higher %time-in-range in the first (83.2% vs 78.1%; p=0.06), second [88.7% vs 80.5%; p=0.02] and third trimester (90.2% vs 79.5%; p=0.07), compared to the blinded group. Conversely, the unblinded group had lower %time-below-range in the first trimester (15.4% vs 21.2%; p=0.06), and early second trimester (8.8% vs 16.9%; p=0.05]. No significant differences were observed with the %time-above-range, mean, standard deviation, Mean Amplitude Glycaemic Excursion and % Coefficient Variation across all trimesters. Conclusion: CGM feedback, coupled with better glycaemic control (higher %TIR and low %TBR) indicates its’ potential use in combination with appropriate patient education for promoting better glucose control during pregnancy.

Castleman Disease Presenting as Lymphadenopathy in a Female with Systemic Lupus Erythematosus: A rare case report

A document by HaoRan Fu. Click on the document to view its contents.

Objective - To analyze the effectiveness of minimal stimulation protocol of IVF treatment for patients with severe diminished ovarian reserve (DOR), especially for whom failed with several cycles of conventional stimulation IVF protocols previously. Design, setting and sample – A single center retrospective cohort study of undergoing IVF during January 1st, 2005 to December 31st, 2021. A total of 1,111 conventional stimulation cycles and 14,139 cycles of minimal stimulation IVF cycles were analyzed. Methods - Women who had undergone minimal stimulation protocol for IVF treatment and who met the study design were admitted to the study. Patients who met the study design undergone conventional stimulation IVF cycles were also included as control. Basic characteristics and clinical outcomes were all recorded and matched for the analysis of the effectiveness of minimal stimulation IVF treatment. Main Outcome Measures – The number of oocytes retrieved, the number of embryos obtained and gonadotrophin stimulation dosage, stimulation days and clinical pregnancy rates were analyzed. Results - In 16 years, a total of 14,139 cycles of minimal stimulation IVF cycles were included into this study in order to compare the effectiveness of the minimal stimulation cycles and the conventional stimulation cycles. Although a smaller number of oocytes was retrieved in the minimal stimulation cycles compared with the conventional stimulation cycles (1.39 vs 2.26, p<0.05), the similar pregnancy rates were obtained in both groups (16.93% vs 18.99%). There were also no differences in live birth and miscarriage rates in the minimal stimulation cycles compared with the conventional cycles. Further analysis indicates that the clinical outcomes were reduced significantly after two cycles of conventional stimulation cycles with high dosage of gonadotropins in those women with DOR. Conclusion- Cumulative minimal stimulation IVF treatment is an effective alternative for women with severe DOR. If a woman with DOR is seeking fertility treatment, it is wise to turn to minimal stimulation protocol after no more than two cycles of the conventional stimulation.

Type of the Paper (Article)The photothermal conversion and UV resistance of silk fabrics being achieved through surface modification with C@SiO2 nanoparticlesAbstract: With the improvement in people’s living standards, the development and application of smart textiles are receiving increased attention. In this study, a carbon nanosurface was successfully coated with a SiO2 layer to form C@SiO2 nanomaterials, which improved the dispersion of carbon nanomaterials in aqueous solution and enhanced the absorption of light by the carbon nanoparticles. C@SiO2 nanoparticles were coupled on the surface of silk fabric with a silane coupling agent KH570 to form C@SiO2 nanosilk fabric. The silk fabric that had undergone such surface modification was endowed with a special photothermal function. The results obtained with scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and infrared spectroscopy (FTIR) showed that C@SiO2 nanoparticles were successfully modified on the surface of the silk fabric. In addition, under the irradiation of near-infrared light with a power of 20 W and a wavelength of 808 nm, the C@SiO2 nanosilk fabric was rapidly warmed from 23 °C to 60 °C within 30 s. After subjecting the functional fabric to hundreds of photothermal experiments and multiple washes, the photothermal efficiency remained largely unchanged and proved to be durable and stable. In addition, the thermogravimetric (TG) analysis results showed that the C@SiO2 nanoparticles contributed to the thermal stability of the silk fabric. The UV transmittance results indicated that C@SiO2 nanofabric is UV-resistant. The silk modification method developed in this study is low-cost, efficient, and environmentally friendly. It has some prospects for future applications in the textile industry.Keywords:C@SiO2nanomaterials; photothermal conversion; UV resistance; clean production;Gang Deng 1,Lu Yao 1, Yuanyuan Yang 1,Song Lu 1，and Guohua Wu 1, *1 School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212018, China; jayderek@foxmail.com. yaolull@163.com. 1465329421@qq.com. 269662442@qq.com* Correspondence: ghwu@just.edu.cn; Tel.: (86)511-85616840.

Title: Acute Myeloid Leukemia with Unreported Translocation (x; 3) (q24; p13): A case report

An Unusual Case of Isolated Native Pulmonic Valve Enterococcus faecalis Endocarditis

Knowledge of individual age can help both in-situ and ex-situ conservation programs to design more efficient and suitable management plans for targeted wildlife species. DNA methylation is one of the epigenetic aging markers that has emerged as a promising tool that can estimate age with high accuracy using only a tiny amount of biological material, which can be collected in a minimally invasive way. Although the conservation of Felidae species has received great attention, studies rarely focus on the development of age estimation models. Here, we sequenced five genetic regions and used 4–25 selected CpG sites to build age estimation models with several machine learning methods, using blood samples of seven Felidae species—ranging from small to big, and domestic to endangered species: domestic cats (Felis catus, 139 samples), Tsushima leopard cats (Prionailurus bengalensis euptilurus, 84 samples), and five Panthera species (96 samples). The models built achieved satisfactory accuracy—the mean absolute deviation of the best models was 1.80, 1.30, and 1.55 years in domestic cats, Tsushima leopard cats, and Panthera spp., respectively. Our models in domestic cats and Tsushima leopard cats were applicable to all individuals regardless of health conditions and sex, indicating high applicability of our models to samples collected from diverse situations, e.g., rescued individuals in the context of conservation. We also showed the possibility of developing universal age estimation models for the five Panthera spp. using two of the five genetic regions, suggesting an even lower cost to use our models for future applications.

Backgrounds: The absence of a gold-standard treatment for COVID-19 infection encourages clinicians to benefit from multipotential medications in the treatment of COVID-19. The current controlled randomized clinical trial tried to evaluate the efficacy and safety of pentoxifylline (PTX) as an adjuvant therapy in moderate to severe COVID-19 infection. Methods: In this randomized controlled clinical trial, two groups of hospitalized patients with moderate to severe COVID-19 infection were randomized by the block randomization method to either receive standard protocol therapy or standard protocol therapy plus pentoxifylline 400 mg TDS for 14 days. Results: The results showed a greater improvement in the proinflammatory biomarkers in the intervention group. Oxygen saturation, hemoglobin, and platelet levels were also improved to a higher level among pentoxifylline recipients. The mortality rate was reported 4% and 32% in the intervention and control groups, respectively. One out 13 patients with severe COVID-19 infection expired in the intervention group, while 20 out of 28 patients expired in the control group, showing about 10 times higher mortality rate compared to the pentoxifylline recipients. Conclusion: Pentoxifylline increased the survival rate of COVID-19 patients and played as a preventive role for COVID-related mortality and morbidity such as acute respiratory distress syndrome.

The genetic composition of founding populations plays a key role in determining invasion success. Despite this fact, the role of genetic variation on the potential distribution of invaders has rarely been investigated. Here, we integrate genomic data into ecological niche models (ENMs) to predict the distribution of globally invasive common ragweed (Ambrosia artemisiifolia) to Australia. We identified three genetic clusters of ragweed and used these clusters to construct separate ENMs. The predicted distribution of ragweed in Australia changed depending on the genetic composition and continent of origin of the source population. By quantifying this change, we identified source populations most likely to expand the ragweed distribution. As prevention remains the most effective method of invasive species management, our work provides a valuable way of ranking the threat posed by different populations to better inform management decisions.

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A document by Bayraktar HS. Click on the document to view its contents.

Cold stress restricts plant development seriously, resulting in heavy agricultural losses. We found a critical transcription factor network in Medicago ruthenica is involved in plant adaptation to low temperature. APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factor MrERF039 was transcriptionally induced by cold stresses in M. ruthenica. We established an agrobacterium-mediated transient expression system and found that MrERF039 plays an active role in the cold response of M. ruthenica. Overexpression of MrERF039 significantly increased the soluble sugar content, which was eventually expressed as the accumulation of glucose and maltose. Electrophoretic mobility shift assays (EMSA) and yeast monohybrid crosses showed that MrERF039 could bind to the DRE cis-acting element on the MrCAS15A promoter. Additionally, the methyl group of the 14th amino acid in the MrERF039 protein was required for the binding. Transcriptome results analysis showed that the MrERF039 gene acted as a sugar molecular switch, regulating many sugar transporters and sugar metabolism related genes. In addition, we found that MrERF039 can directly regulate the expression of β-amylase gene, UDP glycosyltransferase gene and C2H2 zinc finger protein gene. And the significant increase in glucose and maltose content may be caused by the breakdown of starch degraded by β-amylase. In conclusion, these findings suggest that high expression of the MrERF039 gene can significantly improve the cold tolerance of M. ruthenica root tissues during cold acclimation. These provides a new theoretical basis and candidate genes for breeding new legume forage varieties with high resistance, high yield and high protein.

The strategy of combining phytostabilization and biochar amendment was suggested as an alternative for selenium (Se) bioremediation in contaminated soils. The current study aimed to test the performance of activated biochar as an amendment for the phytostabilization of selenium in soil by Phleum sp. For this, Phleum sp. had been grown in Se-contaminated soil mixed with activated biochar which was produced by the pyrolysis of wood residues and the activation of biochar at 900°C in presence of superheated steam. Results showed that Se immobilization in soil was enhanced by the addition of activated biochar owing to its improved physicochemical structure compared to non-modified biochar. In parallel, activated biochar contributed to the improvement of soil fertility by increasing pH and organic matter. The bioaccumulation factor (BAF) of Se in absence of activated biochar and biochar amendment was 8.7, which suggests the suitability of Phleum plant species as Se secondary accumulator species to be further used in a Nordic context. Se plant uptake was positively correlated to Se level in soil, pH, redox potential, organic matter, cations, metals (Al, Cr, Fe, Mn, Co, Pb) and anions (Cl, SO 4). However, Se bioavailability for plant uptake was reduced due to Se immobilization in soil by activated biochar which reduced the translocation of Se from soil to plant and then its bioaccumulation in plant. Thus, combination of activated biochar and Phleum Se-accumulator plant was validated as an efficient solution for Se remediation in contaminated soil which could be applied at large scale under cold climates.

A document by Hamid Mottaghi Golshan. Click on the document to view its contents.

INTRODUCTIONOver-the-counter (OTC) drugs have sometimes been used for suicide attempt and it was reported that among OTC drugs used in adults the most common was acetaminophen in emergency hospitals in Canada [1]. Other OTC analgesics in their cases included acetylsalicylates, ibuprofen and others, and deaths were observed in case of acetaminophen and acetylsalicylate intoxications [1]. Respiratory insufficiency could occur in acetylsalicylate intoxications by way of central nervous system involvements, metabolic disorders or vomiting-induced suffocation [1]. Severe respiratory insufficiency will cause miscellaneous neurological manifestations because of secondary hypoxic-ischemic encephalopathy (HIE). In these cases the cerebellum is one of the vulnerable sites [2, 3]. However, exclusive severe cerebellar atrophy associated with remarkable cerebellar symptoms after respiratory insufficiency has not been reported probably because patients with HIE usually show extensive brain lesions as a whole.We experienced a patient who exhibited exclusively marked cerebellar dysfunction and atrophy on magnetic resonance imaging three years after salicylate poisoning and respiratory insufficiency. Cerebellar atrophy was considered to be induced in these unique clinical situations, although its definite pathophysiology remained unknown.

Background: The β3 adrenergic receptor (AR) plays a crucial role in regulating lipolysis and thermogenesis in visceral adipose tissue and is an important drug development target for obesity and diabetes. However, there is no structural information available for the mouse β3 AR, and its selectivity mechanism is poorly understood. Objective: To address this, the study aimed to construct and validate a 3D homology model of the mouse β3 AR using computational methods and multiple software tools. Methods: we constructed and validated a 3D homology model of the mouse β3 AR using the β3 ADR amino acid sequence of Mus musculus from NCBI and identified possible templates using protein BLAST. We characterized the protein and aligned the sequence with Clustal Omega to identify conserved regions. The homology model was constructed using three different software/servers: SWISS Model, Phyre2.0, and iTASSER, and validated using various techniques. Results: The β3 AR model comprises 400 amino acid residues, exhibits a theoretical pI of 9.57, instability index of 0.57, aliphatic index of 98.35, and GRAVY value of 0.289. Phyre2.0 constructed the most accurate β3 AR model using c2rh1A as a template, with an ERRAT score of 84.076. The Ramachandran plot revealed 93.2% of residues in the favored regions. Conclusion: The study highlights the significance of homology modeling as a computational method for predicting protein 3D structure and emphasizes the importance of comparing and evaluating models generated from multiple templates and software tools. The β3 AR model generated in this study may facilitate future research on the structure and function of the β3 AR, potentially leading to the development of more effective drugs for obesity and diabetes.

The core metabolic reactions of life drive electrons through a class of redox protein enzymes, the oxidoreductases. The energetics of electron flow is determined by the redox potentials of organic and inorganic cofactors as tuned by the protein environment. Understanding how protein structure affects oxidation-reduction energetics is crucial for studying metabolism, creating bioelectronic systems, and tracing the history of biological energy utilization on Earth. We constructed ProtReDox ([https://protein-redox-potential.web.app](https://protein-redox-potential.web.app)), a manually curated database of experimentally determined redox potentials. With over 500 measurements, we can begin to identify how proteins modulate oxidation-reduction energetics across the tree of life. By mapping redox potentials onto networks of oxidoreductase fold evolution, we can infer the evolution of electron transfer energetics over deep-time. ProtReDox is designed to include user-contributed submissions with the intention of making it a valuable resource for researchers in this field.