RETRACTED: PO-04-037 ARTIFICIAL INTELLIGENCE FOR ANALYSIS OF MOBILE CARDIAC TELEMETRY.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This abstract has been retracted at the request of the Authors; please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The abstract was withdrawn after being accepted for presentation at Heart Rhythm, the annual meeting of the Heart Rhythm Society, because there was substantial content development after it had been submitted, both in terms of more in-depth analyses and quantitative changes due to final adjudication of events. The Authors intended to withdraw the abstract from publication as well but omitted to do so. The Authors apologize for the inconvenience caused by this oversight.

Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

A strategy for the controllable generation of organic superbases from benchtop-stable salts.

Organic superbases are a distinct class of strong base that enable numerous modern reaction applications. Despite their great synthetic potential, widespread use and study of superbases are limited by their air sensitivity and difficult preparation. To address this, we report air-stable carboxylate salts of BTPP and P2-t-Bu phosphazene superbases that, when added to solution with an epoxide, spontaneously generate freebase. These systems function as effective precatalysts and stoichiometric prereagents for superbase-promoted addition, substitution and polymerization reactions. In addition to improving the synthesis, shelf stability, handling and recycling of phosphazenes, this approach enables precise regulation of the rate of base generation in situ. The activation strategy effectively mimics manual slow addition techniques, allowing for control over a reaction's rate or induction period and improvement of reactions that require strong base but are also sensitive to its presence, such as Pd-catalyzed coupling reactions.

Long-Term Outcomes Following the Ross Procedure in Neonates and Infants: A Multi-Institutional Analysis.

OBJECTIVES: For neonates and infants with aortic valve pathology, the Ross procedure has historically been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking. METHODS: The international, multi-institutional Ross Collaborative included six tertiary-care centers. Infants who received a Ross operation between 1996-2016 (allowing a minimum five years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function. RESULTS: Primary diagnoses for the 133 patients (n=30 neonates) included isolated aortic stenosis (AS; 14%, n=19), Shone complex (14%, n=19), and AS+other (excluding Shone complex; n=95, 71%) including arch obstruction (n=55), left ventricular hypoplasia (n=9), and mitral disease (>moderate stenosis or regurgitation, n=31). At the time of Ross, median age was 96 (IQR 36-186) days and median weight was 4.4 (3.6-6.5) kg. In-hospital mortality occurred in 13/133 (10%) patients (4/30 [13%] neonates). Post-discharge mortality occurred in 10/120 (8%) patients at a median 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4-5 standard deviations above normal at 2-3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/LVOT reintervention was required in 5/120 (4%) patients at a median 10.3 [4.1-12.8] years. Freedom from >moderate neoaortic regurgitation (AR) was 86% at 15 years. CONCLUSIONS: Neonates and infants experience excellent post-discharge survival and long-term freedom from autograft reintervention and AR following Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease.

Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain.

Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory neurons exhibited greater changes in translation after peripheral nerve injury compared to excitatory neurons. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV + ) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV + neurons decreased their intrinsic excitability and spiking activity, whereas reducing translation in spinal PV + neurons prevented the nerve injury-induced decrease in excitability. Thus, translational control mechanisms in the spinal cord, particularly in inhibitory neurons, play a role in mediating neuropathic pain hypersensitivity.

Cervicothoracic ventral-dorsal rhizotomy for treatment of brachial hypertonia in cerebral palsy.

PURPOSE: Cervicothoracic ventral-dorsal rhizotomy (VDR) is a potential treatment of medically refractory hypertonia in patients who are not candidates for intrathecal baclofen, particularly in cases of severe upper limb hypertonia with limited to no function. A longitudinal cohort was identified to highlight our institutional safety and efficacy using cervicothoracic VDR for the treatment of hypertonia. METHODS: Retrospective data analysis was performed for patients that underwent non-selective cervicothoracic VDR between 2022 and 2023. Non-modifiable risk factors, clinical variables, and operative characteristics were collected. RESULTS: Six patients (three female) were included. Four patients underwent a bilateral C6-T1 VDR, one patient underwent a left C7-T1 VDR, and another underwent a left C6-T1 VDR. Three patients had quadriplegic mixed hypertonia, one patient had quadriplegic spasticity, one patient had triplegic mixed hypertonia, and one patient had mixed hemiplegic hypertonia. The mean difference of proximal upper extremity modified Ashworth scale (mAS) was - 1.4 ± 0.55 (p = 0.002), and - 2.2 ± 0.45 (p < 0.001) for the distal upper extremity. Both patients with independence noted quality of life improvements as well as increased ease with dressing and orthotics fits. Caregivers for the remaining four patients noted improvements in caregiving provision, mainly in dressing, orthotics fit, and ease when transferring. CONCLUSION: Cervicothoracic VDR is safe and provides tone control and quality of life improvements in short-term follow-up. It can be considered for the treatment of refractory hypertonia. Larger multicenter studies with longer follow-up are necessary to further determine safety along with long-term functional benefits in these patients.

Electrostatic Surface Potentials and Chalcogen-Bonding Motifs of Substituted 2,1,3-Benzoselenadiazoles Probed via 77Se Solid-State NMR Spectroscopy.

Chalcogen bonds (ChB) are moderately strong, directional, and specific non-covalent interactions that have garnered substantial interest over the last decades. However, ChB applications are currently hampered by a lack of methods to characterize and control chalcogen bonds. We report on the influence of various substituents (halogens, cyano, and methyl groups) on the observed self-complementary ChB networks of 2,1,3-benzoselenadiazoles. From molecular electrostatic potential calculations, we show that the electrostatic surface potentials (ESP) of the σ-holes on selenium are largely influenced by the electron-withdrawing character of these substituents. Structural analyses via X-ray diffraction reveal a variety of ChB geometries and binding modes that are rationalized via the computed ESP maps, although the structure of 5,6-dimethyl-2,1,3-benzoselenadiazole also demonstrates the influence of steric interactions. 77Se solid-state magic-angle spinning NMR spectroscopy, in particular the analysis of the selenium chemical shift tensors, is found to be an effective probe able to characterize both structural and electrostatic features of these self-complementary ChB systems. We find a positive correlation between the value of the ESP maxima at the σ-holes and the experimentally measured 77Se isotropic chemical shift, while the skew of the chemical shift tensor is established as a metric which is reflective of the ChB binding motif.

High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.

Bacterial diversity and geomicrobiology of Winter Wonderland ice cave, Utah, USA.

The Winter Wonderland ice cave, located at an elevation of 3140 m above sea level in the Uinta Mountains of northern Utah, USA, maintains a constant sub-zero temperature. Seasonal snowmelt and rain enter the cave, freeze on the surface of the existing ice, and contribute to a 3-m-thick layered ice mass. This ice mass contains organic matter and cryogenic cave carbonates (CCCs) that date back centuries. In this study, samples of ice, liquid water, and exposed CCCs were collected to examine the bacterial communities within the cave and to determine if these communities vary spatially and between sample types. Flow cytometry showed that cell counts are an order of magnitude higher in liquid water samples than in ice. Epifluorescence microscopy and scanning electron microscopy imaging revealed potential coccoid and bacillus microbial morphologies in water samples and putative cells or calcite spherules in the CCCs. The diversity of bacteria associated with soil, identified through sequence-based analysis, supports the hypothesis that water enters the cave by filtering through soil and bedrock. A differential abundance of bacterial taxa was observed between sample types, with the greatest diversity found in CCCs. This supports a geomicrobiological framework where microbes aggregate in the water, sink into a concentrated layer, and precipitate out of the ice with the CCCs, thereby reducing the cell counts in the ice. These CCCs may provide essential nutrients for the bacteria or could themselves be products of biomineralization.

Sodium Intake and Incident Atrial Fibrillation in Individuals With Vascular Disease.

Importance: Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality. Objective: To study the association between sodium intake and incident atrial fibrillation (AF). Design, Setting, and Participants: This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024. Exposure: Estimated sodium intake from a morning fasting urine sample (Kawasaki formula). Main Outcomes and Measures: The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines. Results: A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed (P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake. Conclusions and Relevance: In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Optical Relay Sensing of Cryptochiral Alcohols Displaying α-, ß-, γ- and δ-Stereocenters or Chirality by Virtue of Isotopic Substitution.

A reaction-based optical relay sensing strategy that enables accurate determination of the concentration and enantiomeric ratio (er) of challenging chiral alcohols exhibiting stereocenters at the α-, ß-, γ- or even δ-position or hard-to-detect cryptochirality arising from H/D substitution is described. This unmatched application scope is achieved with a conceptually new sensing approach by which the alcohol moiety is replaced with an optimized achiral sulfonamide chromophore to minimize the distance between the covalently attached chiroptical reporter unit and the stereogenic center in the substrate. The result is a remarkably strong, red-shifted CD induction that increases linearly with the sample er. The CD sensing part of the tandem assay is seamlessly coupled to a redox reaction with a quinone molecule to generate a characteristic UV response that is independent of the enantiopurity of the alcohol and thus allows determination of the total analyte concentration. The robustness and utility of the CD/UV relay are further verified by chromatography-free asymmetric reaction analysis with small aliquots of crude product mixtures, paving the way toward high-throughput chiral compound screening workflows which is a highly sought-after goal in the pharmaceutical industry.

Focal selective dorsal rhizotomy and concurrent deformity correction: a combined approach.

OBJECTIVE: Selective dorsal rhizotomy (SDR) is a neurosurgical procedure to reduce spasticity in children with cerebral palsy and spastic diplegia. The authors developed a procedure called focal SDR for children with spasticity predominantly in the L5 or S1 motor distribution, which can be combined with orthopedic correction of fixed soft-tissue or bony deformity. The authors describe in detail the technique of minimally invasive focal SDR and propose selection criteria. METHODS: The authors conducted a retrospective study of patients who underwent focal SDR at their institution and underwent baseline and 1-year postoperative 3D gait analysis. Modified Ashworth scale (MAS) and Gait Deviation Index (GDI) scores were the primary outcome measures. RESULTS: Ten patients met the study criteria, all with an underlying diagnosis of cerebral palsy. All underwent focal SDR at the unilateral or bilateral S1 level, and 4 additionally underwent focal SDR at the L5 level unilaterally or bilaterally. All but 1 patient underwent concurrent orthopedic surgery. The improvement in spasticity of the plantar flexors, as measured by the MAS score, was 2.2 (p < 0.001). In the patients who underwent L5 focal SDR, there was an improvement in the hamstring MAS score of 1.4 (p = 0.004). The mean improvement in the GDI score following focal SDR was 11 (range -6 to 29, p < 0.001). CONCLUSIONS: Focally impairing spasticity in the gastrocsoleus complex and/or hamstrings muscle group in the setting of less functionally impactful proximal tone is extremely common in cerebral palsy. The novel technique of focal SDR, combined with orthopedic intervention, improves spasticity scores and overall gait mechanics. Further investigation is warranted to define the ideal candidacy and outcomes.

Ligand-based design of [18F]OXD-2314 for PET imaging in non-Alzheimer's disease tauopathies.

Positron emission tomography (PET) imaging of tau aggregation in Alzheimer's disease (AD) is helping to map and quantify the in vivo progression of AD pathology. To date, no high-affinity tau-PET radiopharmaceutical has been optimized for imaging non-AD tauopathies. Here we show the properties of analogues of a first-in-class 4R-tau lead, [18F]OXD-2115, using ligand-based design. Over 150 analogues of OXD-2115 were synthesized and screened in post-mortem brain tissue for tau affinity against [3H]OXD-2115, and in silico models were used to predict brain uptake. [18F]OXD-2314 was identified as a selective, high-affinity non-AD tau PET radiotracer with favorable brain uptake, dosimetry, and radiometabolite profiles in rats and non-human primate and is being translated for first-in-human PET studies.

In Search of a Common Language: The Standardized Electrode Nomenclature for Stereoelectroencephalography Applications.

PURPOSE: Stereoelectroencephalography (SEEG) is widely performed on individuals with medically refractory epilepsy for whom invasive seizure localization is desired. Despite increasing adoption in many centers across the world, no standardized electrode naming convention exists, generating confusion among both clinical and research teams. METHODS: We have developed a novel nomenclature, named the Standardized Electrode Nomenclature for SEEG Applications system. Concise, unique, informative, and unambiguous labels provide information about entry point, deep targets, and relationships between electrodes. Inter-rater agreement was evaluated by comparing original electrode names from 10 randomly sampled cases (including 136 electrodes) with those prospectively assigned by four additional blinded raters. RESULTS: The Standardized Electrode Nomenclature for SEEG Application system was prospectively implemented in 40 consecutive patients undergoing SEEG monitoring at our institution, creating unique electrode names in all cases, and facilitating implantation design, SEEG recording and mapping interpretation, and treatment planning among neurosurgeons, neurologists, and neurophysiologists. The inter-rater percent agreement for electrode names among two neurosurgeons, two epilepsy neurologists, and one neurosurgical fellow was 97.5%. CONCLUSIONS: This standardized naming convention, Standardized Electrode Nomenclature for SEEG Application, provides a simple, concise, reproducible, and informative method for specifying the target(s) and relative position of each SEEG electrode in each patient, allowing for successful sharing of information in both the clinical and research settings. General adoption of this nomenclature could pave the way for improved communication and collaboration between institutions.

Facial Hair in Hair Restoration Surgery: Beard Transplantation and Beard-To-Scalp Hair Restoration.

Restoration of the beard region has become an important component of hair restoration surgery due to increased awareness of its natural-appearing results. In the author's experience performing more than 700 primary beard hair transplants and tens of reparative procedures, key aesthetic steps include proper graft dissection so that one- and two-hair grafts contain a minimal cuff of surrounding skin, acute angulation and appropriate direction of recipient sites using the smallest possible recipient-site blades, and aesthetic design.