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Closed-loop control and experimental study of rotor vibration considering track constraints
No full textTo address issues such as excessive 1/rev low-frequency vibration of the rotor and track split caused by blade dissimilarity， a closed-loop vibration control algorithm for rotors based on blade track constraints was developed. Firstly， a rotor aeroelastic coupling model with flexible blades was established， with parameters set to simulate the dissimilarity of blades in engineering applications， thereby generating track split phenomena and vibration imbalance characteristics. Secondly， taking the harmonic components of rotor vibration as the control objective， the collective pitch variation of individual blades as the control input， and the track difference as the constraint condition， a set of constrained optimization problems was constructed to solve for the optimal control inputs. Then， through numerical simulations， the control algorithm without track constraints was compared， and the results demonstrate that introducing track constraints not only significantly reduced the amplitude of low-frequency vibrations but also confined the track difference within a specified range， verifying the effectiveness of the constrained control algorithm. Finally， further experimental validation was conducted by establishing a rotor system test platform， adapting the control algorithm into a Simulink model， and integrating corresponding hardware devices to build a software-hardware architecture. Execution of the control algorithm under different flight conditions shows that vibrations were reduced by over 60% in all cases， with track differences constrained near the set value and achieving a maximum reduction of 73%
CITED2 is a druggable epigenetic switch coupling neuronal maturation to regenerative decline
No full textNeuronal maturation involves a tightly regulated cessation of growth and acquisition of polarity, ultimately leading to synapse formation. While essential for circuit stability, maturation marks the loss of regenerative capacity after central nervous system (CNS) injury. The molecular programs coupling maturation to regenerative decline remain incompletely understood. Here, we show that the transcriptional and epigenetic signatures enabling axon growth in dorsal root ganglion (DRG) neurons are lost as they transition from immature, non-polarized cells to mature, pseudo-unipolar neurons. We identify the transcriptional co-regulator CITED2 as a key epigenetic switch, active in immature and regenerating DRG neurons but silent after non-regenerative spinal cord injury (SCI). Cited2 overexpression reactivates growth programs, enhancing regeneration in vivo after SCI. Mechanistically, CITED2 reinstates developmental epigenetic and transcriptional profiles, decoupling maturation from regenerative failure. Pharmacogenomic screening identified CITED2 as a target of the clinically approved HDAC inhibitor Panobinostat, which promoted axonal growth, sprouting, and functional recovery post-injury. These findings position CITED2 as a key regulator of sensory neuron plasticity and a novel therapeutic target for CNS repair
Endometrial immune cell profile at the time of frozen embryo transfer as prognostic indicator of live birth
Get PDFIntroduction: Endometrial receptivity is essential for implantation in both natural and ART cycles, yet the cellular and molecular environment of the endometrium during this window remains poorly characterized. While cytokines affecting implantation have been studied, data on immune cell subtypes in the endometrium are limited. The objective of this study was to determine the association between endometrial immune cell profile at the time of transfer and live birth in patients undergoing frozen embryo transfer (FET) using the index cycle.Methods: This exploratory prospective observational cohort study (IRB#20190139) included 48 patients undergoing a hormone replacement FET cycle between May 2022 and May 2024. After ultrasound-guided FET, the catheter tip was rinsed in IMDM + 10% FBS, centrifuged, and stained for CD45, CD3, CD19, CD4, CD8, γδ TCR, CD25, CD127, CD66b, CD14, CD16, and CD56. The primary outcome was live birth. Secondary outcomes included miscarriage, biochemical pregnancy, and ectopic pregnancy.Results: Elective single embryo transfer was performed for all the patients. There were 24 live births (50%), four miscarriages (8.3%), and three biochemical pregnancies (6.3%). There was no significant difference in demographics of patients that had a live birth compared to those who did not achieve implantation. There was an increased percentage of γδ T cells in the group of live birth compared to non-pregnant group (p=0.019). In contrast, an increased percentage of neutrophils (CD66b+) was noted in patients that did not achieve implantation (p<0.003). Importantly, we found receiver operating characteristic (ROC) curve area under the curve (AUC) of 0.72 with 95% confidence interval (CI) 0.5504 to 0.8989 for γδ T cells and AUC is 0.75 (95% CI 0.5681 to 0.9319) for CD66b+ cells, confirming the overall ability of these two tests to discriminate between patients who will achieve a live birth vs. ones who will have failed implantation.Discussion: Our findings suggest that the uterine immune environment during FET may be associated with implantation outcomes. Characterization of endometrial immune cell profiles could provide insights into biological factors linked to implantation and live birth, although their clinical utility remains to be determined. To our knowledge, this study is among the first to describe associations between immune cell profiles assessed during the index FET cycle and subsequent IVF outcomes, supporting a potential role for endometrial immune composition in pregnancy success
High-dose influenza vaccine augments serological and cellular immunity of older people with HIV
Get PDFHigh-dose influenza vaccine, containing four times more antigen than standard-dose, is recommended for people aged ≥ 65 years, but there is a knowledge gap surrounding its effect in people with HIV (PWH), who remain more vulnerable to serious influenza infections than people without HIV (PWoH) despite virological suppression. The primary goal of this study was to assess whether high-dose improves antibody responses in PWH, with a particular focus on older PWH.
We conducted a study to assess antibody responses to sequential high- versus standard-dose influenza vaccination in PWH. Young (18-40 years) PWoH (n=55) and PWH (n=37); and older (≥ 60 years) PWoH (n=72) and PWH (n=67) received standard-dose during the 2020-2024 seasons and 123 participants, including 41 older PWH, received high-dose the consecutive season. All PWH were virologically suppressed on ART. Hemagglutination inhibition (HAI) titer and HA-specific IgG were analyzed at 0- to 180-days post-vaccination (dpv); T cell activation-induced responses were assessed by flow cytometry.
All groups mounted significant HAI and IgG responses to all vaccine antigens at 28 dpv, after standard- and high-dose vaccination. Responses to A/H1N1 were lower in magnitude and durability in older PWH compared to young PWoH following standard-dose and were not boosted with high-dose, whereas high-dose enhanced A/H3N2 and B/Victoria IgG, and CD4+ T cell responses to all antigens, in older PWH.
Our data demonstrate partial efficacy of high-dose in augmenting antibody responses of older PWH while highlighting limitations in boosting A/H1N1-specific responses.
gov NCT04487041.
NIH grant (5R01AG068110)
Large sarcomatoid chromophobe renal cell carcinoma with tumor thrombus extending into the inferior vena cava: a case report on the challenges and lessons from a fatal outcome
Get PDFThe effect of non-tobacco nicotine on bone healing: a systematic review and application to total joint arthroplasty
No full textBackground: Bone healing and joint repair are complex biological processes impacted by vascular supply, cellular activity, and the local environment of the affected tissues. Nicotine is a widely used substance that can affect multiple processes needed for adequate bone formation and healing after total jointarthroplasty. The purpose of this review was to evaluate the isolated effects of nicotine, independent of tobacco smoke, cigarette combustion products, or vaping aerosols, on bone healing, bone formation, and implant integration relevant to arthroplasty outcomes.Methods: A systematic review was conducted from its inception in May 2024. The review included 62 studies that analyzed nicotine's effects on bone healing, health, or growth in humans and animals. Studies were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) assessment tool.Results: Animal models exposed to nicotine demonstrated delayed bone healing and decreased new bone formation while increasing bone necrosis and chondrocyte density. Nicotine slows osseointegration of titanium implants, reducing implant stability and bone-to-implant contact. Higher doses of nicotineinhibit osteoblast proliferation and increase osteonecrosis. However, at lower doses, nicotine demonstrates anti-inflammatory properties that can partially offset these effects.Conclusions: Nicotine has a dose-dependent effect on bone healing, bone growth, and implant integration, as demonstrated in various animal and in vitro studies. However, the lack of human studies that isolate the effects of nicotine from those of tobacco or cigarette smoke underscores the urgent need for furtherresearch in this area.Keywords: Nicotine, Total Joint Arthroplasty, Systematic Review, Basic Scienc
Serum metabolomic signatures of relapse recovery in early multiple sclerosis
No full textBackground: Relapses in relapsing-remitting multiple sclerosis (RRMS) are acute neuroinflammatory events that shape long-term disease trajectory. Yet, the molecular events during the early recovery period remain poorly characterized, particularly in early, treatment-free disease. Defining these molecular dynamics may clarify mechanisms of repair relevant for understanding early disease progression.Objective: Identify serum metabolomic signatures that discriminate early-stage, untreated RRMS by time from last clinical relapse and capture trends in the recovery period.Methods: Using a cross-sectional cohort study design, we performed untargeted serum metabolomic profiling in 79 RRMS cases (24 weeks) relapse used supervised machine learning (random forest and partial least squares-discriminant analysis) and rank-based tests. Machine learning and rank-based correlation identified monotonic changes across five relapse proximity stages (24 weeks).Results: Multiple metabolites distinguished recent from non-recent relapse (p < 0.05; AUCs 0.72–0.85) and were significantly lower near relapse, including medium-chain acylcarnitines (C6-C10), fatty acid conjugates (hexanoylglycine), microbial-derived aromatics (3-phenylpropionate, 4-vinylcatechol sulfate), and conjugated steroids. Forty-two metabolites had monotonic changes with increasing time from relapse, including 30 decreased and 12 elevated near relapse (p < 0.05). Perturbed pathways involved mitochondrial β-oxidation, tricarboxylic acid cycle flux, membrane lipid remodeling, phase II conjugation, steroid metabolism, and gut-microbial fermentation of polyphenols and aromatic amino acids.Conclusions: Serum metabolomic profiles in early RRMS reflected coordinated biochemical changes following clinical relapse, implicating mitochondrial dysfunction, membrane remodeling, and microbial co-metabolism
2 - Pregnancy of Unknown Location, Early Pregnancy Loss, Ectopic Pregnancy, and Cesarean Scar Pregnancy
No full textPregnancy is an inefficient process. A large proportion of early pregnancies end in miscarriage or early pregnancy failure. Ectopic pregnancies (EPs), those located outside of the proper anatomic boundaries of the uterus, can cause significant maternal morbidity and mortality. This chapter will review the utility of ultrasound (US) in early pregnancy, when its use is essential in the differentiation of normal and abnormal gestation. The evaluation of pregnancy of unknown location, early pregnancy loss/failure, EP, and cesarean scar pregnancy is reviewed. The US findings of normal and abnormal pregnancies, as well as the synthesis of clinical, laboratory, and imaging findings, are described. Emphasis is placed on accurate diagnosis without overdiagnosis, which can place normal pregnancy at risk
Weak Interaction Alters the Photochemical Reactivity of 1,5-Dienes Within a Supramolecular Organic Capsule
No full textWith the goal of testing the role of weak interactions and restricted space on photochemical reactions, intramolecular cross [2+2] addition of six 1,5-dienes (1-6, Scheme 1) was performed within the host octa acid (OA) capsule. Upon excitation of OA-diene complexes in water, photodimerization of the dienes occurred from their excited triplet states generated by energy transfer from the triplet of OA. OA encapsulation eliminates the need for diffusion required for triplet energy transfer and conformer exploration needed to bring the reactive orbitals of the diene closer. The 1,5-diene substituted with para-tolyl group on either side (6) fails to react within OA capsule while in solution it does. Also, the reactivity order was found to depend on the number of para-methyl substituent on the diene, 4>5>>6. Based on molecular dynamics (MD) simulated structures and NOESY correlations we conclude that the para-methyl groups anchor the diene at the narrow ends of the capsule through weak C—H---π interaction. Such anchoring forbid the methyl group to relocate within the capsule during the conversion of the 1,5-diene to more compact [2.1.1] bicyclic product. 1D and 2D NMR spectra confirmed the inclusion of the dienes and their likely structure within the capsule
Low lateral right atrial scar: implications for the diagnosis of cavotricuspid isthmus block following ablation for atrial flutter
No full textHigh density 3D mapping for typical atrial flutter (AFL) ablation can provide a highly detailed voltage and activation map. Post-ablation mapping is typically used to identify cavotricuspid isthmus (CTI). Low voltage areas in the right atrium may yield misleading mapping results.
3D electroanatomic voltage and activation mapping of the right atrium (RA) was performed in 15 patients with typical AFL, using 3D high density mapping with a Halo or Pentaray catheter pre- and post-ablation. Activation and entrainment mapping confirmed CTI dependent AFL in all patients. Mean number of map points was 611 ± 312. Lateral low voltage areas were seen in 11 (73%) patients. Post-ablation activation map during CS pacing (n = 8) demonstrated latest activation on the lateral wall aligned with the low voltage areas (in 6 of 8 patients), and in 3 (27.3%) patients this was later than just lateral to the CTI ablation line, masquerading as a gap in the ablation line. However, bidirectional block was confirmed by differential pacing, widely split double potentials on the ablation line and non-inducibility. Failure to recognize this misleading activation map in 2 patients resulted in delivery of significantly more ablation lesions (34 vs. 19, p = 0.0007).
Areas of low voltage in the low lateral right atrium may lead to slow conduction and delayed activation in this area, in some cases even greater delay than just lateral to the CTI ablation line mimicking a gap in the ablation line. Comparing pre-ablation voltage to post-ablation activation map can identify areas of low voltage with slow conduction. The use of other maneuvers can prove bidirectional block and avoid further unnecessary RF delivery