Systems with non-Hermitian Hamiltonians, especially those exhibiting parity-time ( PT ) symmetry, are of particular interest as they can describe physical open systems with balanced loss into and gain from the environment. In this context, the study of eigenvalue locations and the corresponding phase transitions as a function of the degree of non-Hermiticity γ is accomplished hereby using feedback theory. This approach provides insight about the behavior of these systems and allows generalization of the results for higher-order ones. The proposed ideas are analyzed in detail for a class of coupled resonant circuit chains.

A transition-metal-free one-pot direct synthesis of tetrathiophosphates (R1S)2P(S)SR2 from white phosphorus (P4), through inter-mediate S-sodium S,S-dialkylphosphorotetrathioates (R1S)2P(S)SNa, is presented. In the presence of NaSH, various disulfides such as diaryl disulfides and dialkyl disulfides are easily coupled with P4 to give S-sodium S,S-dialkylphosphorotetrathioates (R1S)2P(S)SNa in almost quantitative yield, which react with alkyl halides in one pot to generate (R1S)2P(S)SR2. Furthermore, S-(2-cyanoethyl)-substituted tetrathiophosphates (R1S)2P(S)SCH2CH2CN are successfully designed as a kind of tetrathiophosphorylation reagents to react with diaryl iodonium salts involving deprotection-dealkylation process.

Background: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. Objective: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years post-tracheostomy placement in children with BPD and tracheostomies. Methods: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and >1 respiratory culture obtained in 36 months post-tracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years post-tracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. Results: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased risk of decannulation (aRR 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. Conclusion: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

Background: To understand the changing trends in reporting of race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years. Methods: A total of 426 articles reporting results of phase 3 lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. Statistical analysis on trends over time on percentage of minority and female participation were performed. Results: Only 137 (32.2%) of the 426 studies analyzed reported race of participants. Among those studies, we found that the mean participation rate of white participants was significantly higher (82.65%) (p < 0.001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), the female participation has improved with time at a rate of 0.65% per year. Conclusions: We found that the reporting and participation of minority races continues to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Especially in African Americans, where the participation in lung cancer phase III clinical trials has declined despite the rising incidence in lung cancer.

The potential of using chatGPT in pharmacometrics was explored in this study, with a focus on developing a pharmacokinetic (PK) model for standard half-life factor VIII. Our results demonstrated that chatGPT can be utilized to accurately obtain typical PK parameters from literature, generate a population PK model in R, and develop an interactive Shiny application to visualize the results. ChatGPT’s language generation capabilities enabled the development of R codes with minimal programming knowledge and helped identify and fix errors in the code. While chatGPT presents several advantages, such as its ability to streamline the development process, its use in pharmacometrics also has limitations and challenges, including the accuracy and reliability of AI-generated data, the lack of transparency and interpretability of AI. Overall, our study demonstrates the potential of using chatGPT in pharmacometrics, but researchers must carefully evaluate its use for their specific needs.

Title: Emerging Therapeutic Options for Sickle Cell Anemia: Enhancing the Current Predominant Treatment

Alteration in the physiological state of the endoplasmic reticulum (ER) leads to the specific response known as unfolded protein response (UPR) or ER stress response. The UPR is driven by three sensor proteins, namely: Inositol Requiring Enzyme 1 (IRE1), Protein Kinase RNA like ER kinase (PERK), and Activating Transcription Factor 6 (ATF6) to restore ER homeostasis. Pathogenic infection can initiate UPR activation; some pathogens can subvert the UPR to promote their survival and replication. Many intracellular pathogens, including Leishmania, can interact and hijack ER for their survival and replication, triggering ER stress and subsequently ER stress response. This review aims to provide a comprehensive overview of the ER stress response in infections with the Leishmania species .

Chikungunya virus (CHIKV) is an arbovirus ( Togaviridae family, Alphavirus genus), first identified in 1953 in Tanzania. In 2005, CHIKV emerged in India, and later caused outbreaks in Southeast Asia, Oceania and the Americas. Some Clinical signs are associated with CHIKV infection include fever and/or concomitant arthralgia, neurological manifestations and death. However, in infections caused by other arboviruses, such as the Dengue virus and West Nile virus, its often observed changes in liver enzymes. This study aims to evaluate the profile of the biochemical markers for kidney and liver injury patients infected with CHIKV in acute phase of infection. We found a significant elevation on the levels of creatinine in CHIKV-infected people, possibly associated with myalgia and indicative of muscle damage. The novelty was the elevated levels of creatinine found during a long period.

Abstract: Background: Cytidine/uridine monophosphate kinase 2 (UMP-CMP kinase 2, CMPK2) has been reported as an antiviral interferon-stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the role of CMPK2 in ZIKV replication remains to be determined. Methods: CMPK2 or retinoic acid inducible gene I (RIG-I) was overexpressed by plasmid transfection or knocked down by siRNA, respectively in A549 cells before the cells were infected with ZIKV. ZIKV RNA and NS1 protein were detected by RT-qPCR and Western Blot, respectively. The activation status of Jak-STAT signaling pathway was determined by the evaluation of the phosphorylation level of STAT1 (p-STAT1, by Western Blot), interferon stimulated response element (ISRE) activity (by dual luciferase assay) and interferon stimulated gene (ISG) expression (by RT-qPCR). Results: We found that ZIKV infection induced CMPK2 expression dependent on RIG-I. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication. Mechanically, we found that CMPK2 inhibited ZIKV replication probably through the activation of Jak/STAT signaling pathway as shown by the increased level of p-STAT1, enhanced activity of ISRE, and the up-regulated expression of some downstream ISGs. Conclusion: ZIKV infection induced CMPK2 expression, which activated the Jak/STAT signaling pathway to inhibit ZIKV replication. Keywords: CMPK2; ZIKV; Jak/STAT signaling pathway

Background: A reduction in the Egg Reappearance Period (ERP) has been suggested to be an early indication of emerging anthelmintic resistance in strongyles. Objective:To measure the strongyle ERP following moxidectin treatment of horses in the southeast of England. Study Design: Prospective study. Methods: Horses with a faecal egg count (FEC) of > 400 strongyle eggs per gram (EPG) in a routine screening sample were enrolled into the study. Moxidectin (400 mcg/kg) was administered per os and FEC tests repeated every 2 weeks for 16 weeks. Results: Forty-eight horses completed the study. The mean EPG prior to treatment was 1047 (range 375 – 2137 EPG). In all but two horses, FEC was 0 EPG 2 weeks after moxidectin administration. In the remaining two, the FECs were 12.5 EPG (97.8-98.3% reductions compared to pre-treatment FEC). At 4 weeks post-treatment, 6 horses had positive FECs (96.6-99.2% reductions). At 6 weeks, 11 horses had positive FECs (83.8% reduction in one horse; >90% reduction in 10). At 8 weeks, 21 horses exhibited positive FECs (<90% reduction in 2). At 10 weeks, 27 horses had positive FECs (<90% in 6). At 12 weeks, 31 horses had positive FECs (<90% reduction in 11). At 14 weeks, 34 horses had positive FECs (<90% reduction in 13). At 16 weeks, 38 horses had positive FECs (<90% reduction in 17). Limitations: Weights of some horses were estimated using weigh tapes rather than a weighbridge. Dosing of the horses with moxidectin was carried out by owners. Conclusions: The results indicated acceptable efficacy of moxidectin at 14 days after treatment; however, the ERP pattern measured across the group suggest that this anthelmintic has a considerably shorter suppressive effect on strongyle egg shedding than measured when it was first introduced ( >13 weeks and up to 24 weeks).

Due to climate warming, forests are expanding to higher elevations and latitudes at the expense of tundra vegetation. While the subsequent increase in aboveground biomass is well-documented, there is much speculation regarding the effects on soil organic carbon (SOC) stocks. To provide insight into the consequences of tree encroachment into treeless tundra, we sampled SOC stocks across 36 forest-tundra ecotones along a 1100 km latitudinal gradient in Norway. Our results show that SOC stocks vary greatly within, as well as among treeline ecotones, and that tree biomass and tree species are not correlated with this variability. Instead, SOC stocks increase with temperature, and vary with slope steepness, slope aspect, and soil parent material. Applying a ‘space-for-time substitution’ perspective, our findings suggest that tree encroachment into tundra is unlikely to have immediate consequences for SOC stocks.

We introduce a fast and easy method of successfully grasping a lead without a free end called the “Wire ThRoUgh Snare Twice (Wire TRUST)” technique in a 49-year-old male patient who required transvenous lead extraction (TLE) and lead replacement due to lead malfunction. Our proposed technique is less difficult than using the Needle’s eye snare because the pigtail catheter is softer and has better operability. The Wire TRUST technique promptly allows a combined superior and femoral approach for TLE, even when the lead tip is difficult to free because of severe adhesion.

Nickel(II) complexes with pyrazole-based ligands are widely employed in catalysis of ethylene oligomerization and subsequent Friedel-Crafts alkylation of toluene. We have prepared ten new nickel(II) dibromide complexes with various substituted bis(azolyl)methanes. They have been characterized using 1H NMR, IR, high resolution mass spectrometry and elemental analysis. The structures of three complexes have been unambiguously established using X-ray diffraction. It was found that these complexes in the presence of Et2AlCl or Et3Al2Cl3 are active both in ethylene oligomerization and Friedel-Crafts alkylation processes (activity up to 3720 kgoligomer·mol[Ni]−1·h−1). The use of Et3Al2Cl3 results in the higher share of alkylated products (up to 60%). Moreover, catalytic systems activated with Et3Al2Cl3 produced small amounts of odd carbon number olefins (up to 0.8%). The Friedel-Crafts alkylation was used as a trap for previously undetected short-chain odd carbon number olefins (C3 and C5).

Turbine wake and local blockage effects are known to alter wind farm power production in two different ways: (1) by changing the wind speed locally in front of each turbine; and (2) by changing the overall flow resistance in the farm and thus the so-called farm blockage effect. To better predict these effects with low computational costs, we develop data-driven emulators of the ‘local’ or ‘internal’ turbine thrust coefficient CT* as a function of turbine layout. We train the model using a multi-fidelity Gaussian Process (GP) regression with a combination of low (engineering wake model) and high-fidelity (Large-Eddy Simulations) simulations of farms with different layouts and wind directions. A large set of low-fidelity data speeds up the learning process and the high-fidelity data ensures a high accuracy. The trained multi-fidelity GP model is shown to give more accurate predictions of CT* compared to a standard (single-fidelity) GP regression applied only to a limited set of high-fidelity data. We also use the multi-fidelity GP model of CT* with the two-scale momentum theory (Nishino & Dunstan 2020, J. Fluid Mech. 894, A2) to demonstrate that the model can be used to give fast and accurate predictions of large wind farm performance under various mesoscale atmospheric conditions. This new approach could be beneficial for improving annual energy production (AEP) calculations and farm optimisation in the future.

The Special Issue brought together papers that highlighted the power of high-throughput sequencing (HTS) data to address classic questions in ecology and evolution, and/or use models/theory to infer key ecological and evolutionary processes, and make predictions, particularly focused on metabarcoding (amplicon) datasets in conjunction with complementary -omics data types. We highlight key papers that show the power of the new technology to address questions related to: (1) community assembly, and the interplay between competition, environmental filtering, and neutral processes, that can be inferred from the data, and how these change according to environmental conditions, and across successional and extended evolutionary time. (2) Interaction networks, and how these can show predictable changes over similar spatial and temporal gradients, providing insights into questions of biotic resilience. Studies also examined (3) cross scale interactions and those involving hosts and their microbiomes, with the critical development being the ease of comparison and integration across scales of organismic complexity, allowing insights at one scale to inform the other. The approach is also amenable to (4) studies of invasive species and biotic homogenization, providing insights of shifts in alpha and beta diversity across a wide range of spatial scales.

Sharks, rays and chimaera form the clade Chondrichthyes, an ancient group of morphologically and ecologically diverse vertebrates that has played an important role in our understanding of gnathostome evolution. Increasingly studies have are seeking to investigate evolutionary processes operating within the chondrichthyan crown group, with the broad aim of understanding the driving forces behind the vast phenotypic diversity observed amongst its constituent taxa. Genetic, morphological and behavioural studies have all contributed to our understanding of phenotypic evolution yet are typically considered in isolation in the context of Chondrichthyes. I argue that integrating these core fields of organismal biology is vital if we are to understand the evolutionary processes operating in contemporary chondrichthyan taxa, and how such processes have contributed to past phenotypic evolution. In light of the global extinction crisis facing this clade, this understanding is crucial if we are to successfully conserve rapidly declining chondrichthyan populations.

A document by Kritika Mishra. Click on the document to view its contents.

Myeloid sarcoma is a rare extramedullary tumoral infiltration of immature myeloid cells and can occur in different sites of the body, without leukemic infiltration A 38-year-old woman patient presented at emergency with a pleural effusion and bicytopenias. In the following days, she worsened with a chylothorax and pancytopenias. Pleural puncture cytologically