Realization of logic gates in bi-directionally coupled nonlinear oscillators.

Implementation of logic gates has been investigated in nonlinear dynamical systems from various perspectives over the years. Specifically, logic gates have been implemented in both single nonlinear systems and coupled nonlinear oscillators. The majority of the works in the literature have been done on the evolution of single oscillators into OR/AND or NOR/NAND logic gates. In the present study, we demonstrate the design of logic gates in bi-directionally coupled double-well Duffing oscillators by applying two logic inputs to the drive system alone along with a fixed bias. The nonlinear system, comprising both bi-directional components, exhibits varied logic behaviors within an optimal range of coupling strength. Both attractive and repulsive couplings yield similar and complementary logic behaviors in the first and second oscillators. These couplings play a major role in exhibiting fundamental and universal logic gates in simple nonlinear systems. Under a positive bias, both the first and second oscillators demonstrate OR logic gate for the attractive coupling, while exhibiting OR and NOR logic gates, respectively, for the repulsive coupling. Conversely, under a negative bias, both the first and second oscillators display AND logic gate for the attractive coupling, and AND and NAND logical outputs for the repulsive coupling. Furthermore, we confirm the robustness of the bi-directional oscillators against moderate noise in maintaining the desired logical outputs.

SARS-CoV-2-Triggered Hemophagocytic Lymphohistiocytosis with Complications of Posterior Reversible Encephalopathy Syndrome.

In this article, we describe a novel case of SARS-CoV-2-associated-hemophagocytic lymphohistiocytosis (HLH) complicated by posterior reversible encephalopathy syndrome (PRES). Initially diagnosed with multisystem inflammatory response in children (MIS-C), the patient received a large corticosteroid dose days before the onset of neurological symptoms. After developing PRES, the patient was treated with antihypertensives, antiepileptics, dexamethasone, and anakinra, leading to neurologic normalization. We propose that given the challenging diagnostic picture of PRES developing in patients with HLH or MIS-C, institutionalized standards for blood pressure management during corticosteroid induction may significantly improve outcomes in patients being treated for hyperinflammatory syndromes who develop neurological symptoms.

Suspected Diphtheria Toxoid and Tetanus Toxoid (dTdap) Booster Vaccine-Induced Postural Orthostatic Tachycardia Syndrome (POTS).

We describe a case of a 40-year-old South Asian woman who presented with symptoms suggestive of postural orthostatic tachycardia syndrome (POTS) following a diphtheria toxoid and tetanus toxoid (dTdap) booster vaccination administered one week prior. The patient's POTS responded favorably to treatment with low-dose fludrocortisone and ivabradine. Clinicians should maintain a high index of suspicion for POTS as a possible vaccine adverse event (VAE) post-dTdap booster inoculation and be aware of appropriate management strategies.

Myocardial Bridging-Induced Acute Coronary Syndrome: A Bridge Too Far.

Recent studies suggest a potential association between myocardial bridging (MB) and accelerated atherosclerotic plaque formation. We describe the case report of a 37-year-old South Asian male with no established risk factors for coronary artery disease (CAD) who presented with a non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) with a coincident widowmaker lesion and severe MB. He was successfully managed with comprehensive guideline-directed medical therapy (GDMT) and urgent percutaneous coronary intervention (PCI) of the culprit lesion, sparing the MB segment. The clinician should be cognizant of MB implicating ACS as a major adverse cardiovascular event (MACE) and its key management strategies.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision ( P =0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group ( P =0.0180). PJK was associated with short fusions when compared with the long fusion group ( P =0.0294) and the interbody group ( P =0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group ( P =0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery ( P =0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

Peroneal Nerve Decompression in Patients with Multiple Hereditary Exostoses: Indications, Complications, and Recurrence.

BACKGROUND: To our knowledge, there have been no studies examining peroneal nerve decompression and proximal fibular osteochondroma excision exclusively in patients with multiple hereditary exostoses (MHE). The purpose of this study was to evaluate the indications, complications, and recurrence associated with nerve decompression and proximal fibular osteochondroma excision in patients with MHE. METHODS: The records on patients with MHE undergoing peroneal nerve decompression from 2009 to 2023 were retrospectively reviewed. Indications, clinical status, surgical technique, recurrence, and complications were recorded and were analyzed using the Fisher exact test, logistic regression, and the Kaplan-Meier method. RESULTS: There were 126 limbs identified in patients with MHE who underwent peroneal nerve decompression. The most common indications were pain over the proximal fibula, tibialis anterior and/or extensor hallucis longus weakness, and dysesthesias and/or neuropathic pain. Seven cases experienced postoperative foot drop as a complication of the decompression and osteochondroma excision. Logistic regression found significant relationships between complications and excision of anterior osteochondromas (odds ratio [OR], 5.21; p = 0.0062), proximal fibular excision (OR, 14.73; p = 0.0051), and previous decompression (OR, 5.77; p = 0.0124). The recurrence rate was 13.8%, and all recurrences occurred in patients who were skeletally immature at the index procedure. The probability of skeletally immature patients not experiencing recurrence was 88% at 3 years postoperatively and 73% at 6 years postoperatively. CONCLUSIONS: Indications for peroneal nerve decompression included neurologic symptoms and pain. The odds of a complication increased with excision of anterior osteochondromas and previous decompression. Recurrence of symptoms following decompression and osteochondroma excision was found exclusively in skeletally immature patients. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

A Lung Cancer Mouse Model Database.

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. Here we established the Lung Cancer Mouse Model Database (LCMMDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors have produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCMMDB aligns 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in GEMMs. Accompanying this resource, we developed a web application that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCMMDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance.

Promises and Perils of Consumer Mobile Technologies in Cardiovascular Care: JACC Scientific Statement.

Direct-to-consumer (D2C) wearables are becoming increasingly popular in cardiovascular health management because of their affordability and capability to capture diverse health data. Wearables may enable continuous health care provider-patient partnerships and reduce the volume of episodic clinic-based care (thereby reducing health care costs). However, challenges arise from the unregulated use of these devices, including questionable data reliability, potential misinterpretation of information, unintended psychological impacts, and an influx of clinically nonactionable data that may overburden the health care system. Further, these technologies could exacerbate, rather than mitigate, health disparities. Experience with wearables in atrial fibrillation underscores these challenges. The prevalent use of D2C wearables necessitates a collaborative approach among stakeholders to ensure effective integration into cardiovascular care. Wearables are heralding innovative disease screening, diagnosis, and management paradigms, expanding therapeutic avenues, and anchoring personalized medicine.

Exploration of field-like torque and field-angle tunability in coupled spin-torque nano oscillators for synchronization.

We investigate the influence of field-like torque and the direction of the external magnetic field on a one-dimensional array of serially connected spin-torque nano oscillators (STNOs), having free layers with perpendicular anisotropy, to achieve complete synchronization between them by analyzing the associated Landau-Lifshitz-Gilbert-Slonczewski equation. The obtained results for synchronization are discussed for the cases of 2, 10, and 100 oscillators separately. The roles of the field-like torque and the direction of the external field on the synchronization of the STNOs are explored through the Kuramoto order parameter. While the field-like torque alone is sufficient to bring out global synchronization in the system made up of a small number of STNOs, the direction of the external field is also needed to be slightly tuned to synchronize the one-dimensional array of a large number of STNOs. The formation of complete synchronization through the construction of clusters within the system is identified for the 100 oscillators. The large amplitude synchronized oscillations are obtained for small to large numbers of oscillators. Moreover, the tunability in frequency for a wide range of currents is shown for the synchronized oscillations up to 100 spin-torque oscillators. In addition to achieving synchronization, the field-like torque increases the frequency of the synchronized oscillations. The transverse Lyapunov exponents are deduced to confirm the stable synchronization in coupled STNOs due to the field-like torque and to validate the results obtained in the numerical simulations. The output power of the array is estimated to be enhanced substantially due to complete synchronization by the combined effect of field-like torque and tunability of the field-angle.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel.

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver.

Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related to the dynamic range of the assays, sensitivity, cost, and technological limitations, transcriptomic approaches are predominantly used in toxicogenomics. Toxicogenomics is being used to understand the mechanisms of toxicity and carcinogenicity, evaluate the translational relevance of toxicological responses from in vivo and in vitro models, and identify predictive biomarkers of disease and exposure. In this session, a brief overview of various transcriptomic technologies and practical considerations related to experimental design was provided. The advantages of gene network analyses to define mechanisms were also discussed. An assessment of the utility of toxicogenomic technologies in the environmental and pharmaceutical space showed that these technologies are being increasingly used to gain mechanistic insights and determining the translational relevance of adverse findings. Within the environmental toxicology area, there is a broader regulatory consideration of benchmark doses derived from toxicogenomics data. In contrast, these approaches are mainly used for internal decision-making in pharmaceutical development. Finally, the development and application of toxicogenomic signatures for prediction of apical endpoints of regulatory concern continues to be area of intense research.

SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset ([~]13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.