Search Results (264)

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent public health threat due to its rapid dissemination and resistance to last-line antibiotics. Cefiderocol (FDC), a novel siderophore cephalosporin, targets resistant Gram-negative pathogens by exploiting bacterial iron uptake mechanisms. However, resistance to FDC is emerging among Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains. This study characterizes a spontaneous FDC-resistant subpopulation (IHC216) derived from a KPC-producing strain (KPNMA216) using comprehensive genomic, transcriptional, and phenotypic analyses. Methods: Given the whole-genome sequencing results, where mutations were identified in genes involved in transcriptional regulation and membrane permeability (ompC) among others, in the present work we further explore their potential implications and conduct a more detailed analysis of the IHC216 genome. A qRT-PCR analysis highlighted significant downregulation of classical siderophore-mediated iron acquisition systems (fepA, cirA, iroN) and upregulation of alternative iron uptake pathways (iucA, fiU), reflecting a switch in iron acquisition strategies. Results: A notable downregulation of bla_KPC-163 correlated with restored susceptibility to carbapenems, indicating collateral susceptibility. Altered expressions of pbp2 and pbp3 implicated adaptive changes in cell wall synthesis, potentially affecting FDC resistance mechanisms. Furthermore, enhanced oxidative stress responses via upregulated sodC expression and increased capsule production were observed. Conclusions: These findings underscore the complex interplay of genetic and transcriptional adaptations underlying FDC resistance, highlighting potential therapeutic vulnerabilities. Full article

Grid-forming (GFM) inverters have recently seen wider adoption in microgrids and inverter-based-resource (IBR)-penetrated grids, and are primarily used to establish grid voltage under a wide array of conditions. In the existing literature, GFM control is almost exclusively applied using voltage-source inverters (VSIs). However, due to the inherent limitations of available semiconductor devices’ current ratings, inverter-side current must be limited in VSIs, particularly during grid-fault conditions. These limitations complicate the real-world application of GFM functionality in VSIs, and complex control methodologies and tuning parameters are required as a result. In the following study, GFM control is instead applied to a buck-type current-source inverter (CSI) using a combination of linear droop-control and finite-control-set (FCS) mode-predictive control (MPC) that will be referred to herein as hybrid model-predictive control (HMPC). The resulting inverter features a simple topology, inherent current limiting capabilities, and a relatively simple and intuitive control structure. Verification was performed on a 1MVA/630V system via MATLAB/Simulink, and the simulation results demonstrate strong performance in voltage establishment, power regulation, and low-voltage ride through under-grid-fault conditions, highlighting its potential as a competent alternative to VSIs in GFM applications, and lacking the inherent limitations and/or complexity of existing GFM control methodologies. Full article

Effective transport strategies are critical for the survival and welfare of juvenile Ictalurus punctatus, but the effects of pre-transport salt bath treatments remain uncertain. In this study, we systematically evaluated the effects of pre-transport salt bath acclimation at 0‰ (S1), 1‰ (S2), 5‰ (S3), and 9‰ (S4) salinity for 30 min on stress resilience and recovery in fingerlings during 12 h of simulated transport and 24 h of recovery. All fish survived, but total ammonia nitrogen (TAN) increased, and pH decreased in all groups, except S3, which showed significantly lower TAN and higher pH (p < 0.05). The S3 and S4 groups showed attenuated increases in serum cortisol and glucose, with S3 exhibiting the fastest return to baseline levels and stable serum sodium and potassium levels. Liver antioxidant enzyme activities in group S3 remained stable, with the lowest malondialdehyde (MDA) accumulation. Integrated biomarker response (IBR) and histological analyses demonstrated that S3 had the lowest systemic stress and tissue damage, whereas S1 and S4 displayed marked cellular disruption. These results indicate that a 5‰ salt bath applied prior to transport may improve water quality, mitigate stress responses, and preserve tissue integrity in juvenile channel catfish. Further studies are needed to confirm these findings in other species and under commercial transport conditions. Full article

Cross-validation and open research on future electric grids, particularly in their stability modeling and dynamic performance, can greatly benefit from high-fidelity, publicly available test cases, since access to dynamic response models of actual grid models is often limited due to legitimate security concerns. This paper presents a methodology for designing and validating the dynamic performance of large, IBR-heavy synthetic grids, that is, realistic but fictitious test cases. The methodology offers a comprehensive framework for creating dynamic models for both synchronous generators (SGs) and inverter-based resources (IBRs), focusing on realism, controllability, and flexibility. For realistic dynamic performance, the parameters in each dynamic model are sampled based on statistical data from benchmark actual grids, considering power system dynamics such as frequency and voltage control, as well as oscillation response. The paper introduces system-wide governor design, which improves the controllability of parameters in dynamic models, resulting in a more realistic frequency response. As an example, multiple case studies on a 2000-bus Texas synthetic grid are shown; these represent realistic dynamic performance under different transmission conditions in terms of frequency, voltage control, and oscillation response. Full article

The transition towards a power system characterized by a reduced presence of synchronous generators (SGs) and an increased reliance on inverter-based resources (IBRs), including wind, solar photovoltaics (PV), and battery storage, presents new operational challenges, particularly when these sources exceed 50–60% of the system’s demand. While current grid-following (GFL) IBRs, which are equipped with fast and rigid control systems, continue to dominate the inverter landscape, there has been a notable surge in research focused on grid-forming (GFM) inverters in recent years. This study conducts a comparative analysis of the practicality and control methodologies of GFM inverters relative to traditional GFL inverters from a system planning perspective. A comprehensive framework aimed at assisting system developers and consulting engineers in the grid-integration of wide-scale renewable energy sources (RESs), incorporating strategies for the deployment of inverters, capacitor banks, and harmonic filters, is proposed in this paper. The discussion includes an examination of the reactive power capabilities of the plant’s inverters and the provision of additional reactive power to ensure compliance with grid interconnection standards. Furthermore, the paper outlines a practical approach to assess the necessity for enhanced filtering measures to mitigate potential resonant conditions and achieve harmonic compliance at the installation site. The objective of this work is to offer useful guidelines and insights for the effective addition of RES into contemporary power systems. Full article

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

Looking toward the future, governments around the world have started to change their energy mix due to climate change. The new energy mix will consist mainly of Inverter-Based Resources (IBRs), such as wind and solar power. This transition from a synchronous to a non-synchronous grid introduces new challenges in stability, resilience, and synchronization, necessitating advanced control strategies. Among these, Grid-Forming (GFM) control techniques have emerged as an effective solution for ensuring stable operations in microgrids and large-scale power systems with high IBRs integration. This paper presents a systematic review of GFM control techniques, focusing on their principles and applications. Using the PRISMA 2020 methodology, 75 studies published between 2015 and 2025 were synthesized to evaluate the characteristics of GFM control strategies. The review organizes GFM strategies, evaluates their performance under varying operational scenarios, and emphasizes persistent challenges like grid stability, inertia emulation, and fault ride-through capabilities. Furthermore, this study examines real-world implementations of GFM technology in modern power grids. Notable projects include the UK’s National Grid Pathfinder Program, which integrates GFM inverters to enhance stability, and Australia’s Hornsdale Power Reserve, where battery energy storage with GFM capabilities supports grid frequency regulation. Full article

Sperm membrane potential (Em) hyperpolarization during capacitation is a functional hallmark of fertilizing ability and has been proposed as a predictive biomarker for conventional in vitro fertilization (IVF) success. However, it is unclear whether Em remains stable across ejaculates over time and can reliably guide assisted reproductive technology (ART) decisions in advance. Thus, we aimed to evaluate the temporal consistency of human sperm Em within individuals and assess its utility as a prognostic marker when measured days or weeks prior to IVF procedures. Em was assessed in capacitated and non-capacitated sperm from normospermic donors at three time points over 28 days, using a fluorometric assay. Capacitated values were compared to a −48.6 mV threshold previously associated with successful fertilization. Intra-donor Em variability and coefficients of variation (CV) were analyzed statistically. Our results showed that Em values exhibited significant intra-donor variability over time (p = 0.007), with approximately half of the donors crossing the −48.6 mV functional threshold across sessions. Capacitated sperm samples showed significantly greater variability than non-capacitated ones, with several donors exceeding a 30% CV cutoff. No consistent correlation was found between CV and mean Em values. While Em remains a promising functional marker when assessed on the day of IVF, its temporal variability undermines its reliability as a predictive tool for ART decisions made in advance. These findings underscore the importance of timing in functional sperm assessments and call for further studies to identify the physiological factors influencing Em stability. Full article

With the increasing level of inverter-based resources (IBRs) in modern power systems, this paper presents a small-signal stability analysis for power systems comprising synchronous generators (SGs) and IBRs. Four types of inverter controls are considered: two grid-following (GFL) controls, with or without grid support functions; droop-based grid-forming (GFM) controls; and virtual oscillator control-based GFM. We also analyze the impact of STATCOM and synchronous condensers on system stability to assess their role in the energy mix transition. With the small-signal dynamic behavior of the major technologies modeled, this paper provides stringent stability assessments using the IEEE 39-bus benchmark system modified to simulate future power systems. The exhaustive test cases allow for (a) assessing the impacts of different types and controls of generation and supplementary grid assets, as well as system inertia and line impedance on grid stability, and (b) elucidating pathways for the stabilization of IBR-dominated power systems. The analysis also indicates that future power systems can be stabilized with only a fraction of the total generation as voltage sources without SGs or significant system inertia if they are well distributed. This study provides insights into future power system operations with a high level of IBRs that can also be used for planning and operation studies. Full article

The increasing penetration of renewable energy sources (RESs) has significantly altered the operational characteristics of modern power systems, resulting in reduced system inertia and fault current capacity. These developments introduce new challenges for maintaining frequency and voltage stability, particularly in low-inertia grids that are dominated by inverter-based resources (IBRs). This paper presents a hierarchical control framework that integrates synchronous condensers (SCs) and grid-forming (GFM) inverters through a leader–follower consensus control architecture to address these issues. In this approach, selected GFMs act as leaders to restore nominal voltage and frequency, while follower GFMs and SCs collaboratively share active and reactive power. The primary control employs droop-based regulation, and a distributed secondary layer enables proportional power sharing via peer-to-peer communication. A modified IEEE 14-bus test system is implemented in PSCAD to validate the proposed strategy under scenarios including load disturbances, reactive demand variations, and plug-and-play operations. Compared to conventional droop-based control, the proposed framework reduces frequency nadir by up to 0.3 Hz and voltage deviation by 1.1%, achieving optimised sharing indices. Results demonstrate that consensus-based coordination enhances dynamic stability and power-sharing fairness and supports the flexible integration of heterogeneous assets without requiring centralised control. Full article

Rising water temperatures due to climate change pose a significant threat to Phoxinus lagowskii, a cold-water fish that is ecologically vital to the high-latitude regions of China. This study assessed heat stress effects on behavioral, hematological, histological, physiological, and molecular responses in P. lagowskii. The critical maximum temperature (CT_max) was determined using the loss of equilibrium (LOE) method, with the CT_max reaching 29 °C. Elevated temperatures lead to an increase in the OBR. Fish were subjected to acute heat stress at 28 °C (below CT_max) for 48 h, with samples collected during the 48 h period. RBC, WBC, HGB, and HCT significantly increased during heat stress but decreased 12 h after heat stress. The levels of serum cortisol and blood glucose after heat stress were significantly higher than those in the control group. After heat stress, the height of the ILCM in the gills increased significantly, and the liver exhibited vacuolar degeneration and hypopigmentation. The activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in the gills initially increased and then decreased over the duration of heat stress. Most enzyme activities (PK, LDH, PFK, and HK) decreased during heat stress, while LPL and HL levels increased, indicating that lipid metabolism was the primary utilization process under heat stress. There was an increase in SOD activity at 12 h, followed by a decrease at 24 h, and an increase in CAT activity under heat stress. Integrated biomarker response (IBR) and principal component analysis (PCA) were employed to synthesize multi-level responses. The IBR values reached their peak at 3 h and 48 h of heat stress. We observed an upregulation of heat shock proteins (Hsp70, Hsp90, and Hsc70) as well as interleukin-10 (IL-10) in response to heat stress. Our findings offer novel insights into the mechanisms underlying the heat stress response in P. lagowskii, thereby enhancing our understanding of the effects of heat stress on cold-water fish. Full article

The rapid growth of inverter-based resources (IBRs) has created a need for new islanding detection methodologies to determine whether an IBR has been disconnected from the transmission grid in some manner (islanded) or remains connected to the transmission grid (grid-connected). Active islanding detection methods inject a signal into the power system to achieve detection. Existing schemes frequently limit consideration to a single node system with one IBR. Schemes tested on multiple IBRs often see interference, with the signals from one IBR disturbing the others, or require intricate communication. Further, several methods destabilize an islanded grid to detect it, preventing a prospective microgrid from remaining in operation while islanded. This work develops an active islanding detection scheme using Pulse Compression Probing (PCP) that is microgrid-compatible and can be used with multiple IBRs without requirement for communication. This active islanding detection scheme can be implemented on existing inverter switching sequences and has a detection time of 167–223 ms, well within the detection time specified by existing standards. The method is verified via electromagnetic transient (EMT) simulation on a modified version of a 34-bus test system. Full article

Background/Objectives: Autologous fat grafting (AFT) has become a widely used technique in breast reconstruction, offering natural aesthetics, tissue integration, and patient satisfaction. However, its clinical outcomes require comparison with implant-based reconstruction (IBR), the most common method in clinical practice. While AFT provides a more natural appearance and avoids foreign body-related complications, issues such as fat resorption, procedural variability, and oncological concerns necessitate further investigation. Additionally, artificial intelligence (AI) has been increasingly integrated into breast imaging and reconstructive planning, improving diagnostic accuracy, procedural optimization, and complication prevention. This study aims to compare AFT and IBR while exploring AI’s role in enhancing breast reconstruction outcomes. Methods: A comprehensive review of clinical studies was conducted to evaluate the advantages, limitations, and oncological implications of AFT versus IBR. AI-driven applications in breast imaging and reconstructive planning were examined for their potential in predicting fat graft retention and optimizing implant selection. Data from systematic reviews and meta-analyses were incorporated to refine reconstruction strategies. Results: AFT offers superior aesthetic outcomes with better tissue integration but presents variability in fat resorption. IBR remains the preferred approach due to its predictability but carries risks of implant-related complications. AI technologies contribute to improved reconstruction planning, enhancing surgical precision and long-term patient outcomes. Conclusions: Optimized patient selection and long-term follow-up are essential for improving breast reconstruction techniques. AI-driven approaches provide valuable tools for enhancing procedural predictability and personalized treatment strategies. Future research should focus on refining AI algorithms and establishing standardized protocols for reconstructive decision-making. Full article

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), continues to pose significant public health challenges due to the toxicity, poor tolerability, and limited efficacy of current treatments. Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) represents a novel therapeutic avenue by leveraging the ubiquitin–proteasome system to selectively degrade essential parasite proteins. This review introduces the conceptual framework of “TrypPROTACs” as a prospective strategy for T. cruzi, integrating a comprehensive analysis of druggable targets across critical biological pathways, including ergosterol biosynthesis, redox metabolism, glycolysis, nucleotide synthesis, protein kinases, molecular chaperones such as heat shock protein 90 (Hsp90), and epigenetic regulators such as T. cruzi bromodomain factor 3 (TcBDF3). It is important to note that no TrypPROTAC compound has yet been synthesized or experimentally validated in T. cruzi; the approach discussed herein remains theoretical and forward-looking. Representative inhibitors for each target class are compiled, highlighting potency, selectivity, and structural features relevant to ligand design. We also examine the parasite’s ubiquitination machinery and compare it to the human system to identify putative E3 ubiquitin ligases. Key aspects of linker engineering and ternary complex stabilization are discussed, alongside potential validation techniques such as the cellular thermal shift assay (CETSA) and bioluminescence resonance energy transfer (NanoBRET). Collectively, these insights outline a roadmap for the rational design of TrypPROTACs and support the feasibility of expanding targeted protein degradation strategies to neglected tropical diseases. Full article

Background and Objectives: Breast reconstruction following mastectomy improves quality of life and psychosocial outcomes, yet it is not consistently performed despite multiple federal mandates. Current data shows decreased reconstruction in minority races, those with a low socioeconomic status, and those holding public health insurance. Many barriers remain misunderstood or unstudied. This study examines barriers to post-mastectomy breast reconstruction to promote a supportive clinical climate by addressing multifactorial obstacles to equitable access to care. Materials and Methods: The California Cancer Registry Data Surveillance, Epidemiology, and End Results (SEER) database and California Health and Human Services Agency Cancer Surgeries Database (2013–2021 and 2000–2021, respectively) were used in this retrospective observational study on mastectomy with immediate breast reconstruction (IBR), delayed breast reconstruction (DBR), or mastectomy only (MO) rates. Data were collected on age, sex, race, insurance type, hospital type, socioeconomic status, and residence. Pearson’s chi-square analysis was performed. Results: We found that 168,494 mastectomy and reconstruction surgeries were performed (82.36% MO, 7% IBR, 10.6% DBR). The 40–49 age group received significantly less MO (38.1%) compared to the 70–74 age group (94.8%, (p = <0.001). Significantly more reconstruction was carried out in patients with private, HMO, or PPO insurance (IBR 75.86%, DBR 75.32%, p = <0.001). Almost all breast surgeries were in urban areas as opposed to rural/isolated rural areas (96.02% vs. 1.55%, p = <0.001). There was no significant difference between races. Of all surgeries, 7.46% were completed in a cancer center with significantly higher rates of IBR. LA County, San Luis Obispo/Ventura County, and Northern CA had significantly more MO than other regions (p = <0.001). Conclusions: Reconstruction rates after mastectomy are low, with only 17.64% of patients undergoing reconstruction. Nationally, 70.5% of patients received MO, with 29.6% undergoing reconstruction. Significant factors positively contributing to reconstruction were private insurance, high SES, cancer center care, and urban residency. Identified barriers include public health insurance enrollment, rural or non-urban residence, older age, low SES, and non-white race/ethnicity, indicating potential monetary influences on care. Full article