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Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number1–3. The natural lanthanide-binding protein lanmodulin (LanM)4,5 is a sustainable alternative to conventional solvent-extraction-based separation6. Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer. X-ray crystal structures illustrate how picometre-scale differences in radius between lanthanum(III) and dysprosium(III) are propagated to Hans-LanM’s quaternary structure through a carboxylate shift that rearranges a second-sphere hydrogen-bonding network. Comparison to the prototypal LanM from Methylorubrum extorquens reveals distinct metal coordination strategies, rationalizing Hans-LanM’s greater selectivity within the rare-earth elements. Finally, structure-guided mutagenesis of a key residue at the Hans-LanM dimer interface modulates dimerization in solution and enables single-stage, column-based separation of a neodymium(III)/dysprosium(III) mixture to >98% individual element purities. This work showcases the natural diversity of selective lanthanide recognition motifs, and it reveals rare-earth-sensitive dimerization as a biological principle by which to tune the performance of biomolecule-based separation processes.

Numerous viruses utilize essential long-range RNA–RNA genome interactions, specifically flaviviruses. Using Japanese encephalitis virus (JEV) as a model system, we computationally predicted and then biophysically validated and characterized its long-range RNA–RNA genomic interaction. Using multiple RNA computation assessment programs, we determine the primary RNA–RNA interacting site among JEV isolates and numerous related viruses. Following in vitro transcription of RNA, we provide, for the first time, characterization of an RNA–RNA interaction using size-exclusion chromatography coupled with multi-angle light scattering and analytical ultracentrifugation. Next, we demonstrate that the 5′ and 3′ terminal regions of JEV interact with nM affinity using microscale thermophoresis, and this affinity is significantly reduced when the conserved cyclization sequence is not present. Furthermore, we perform computational kinetic analyses validating the cyclization sequence as the primary driver of this RNA–RNA interaction. Finally, we examined the 3D structure of the interaction using small-angle X-ray scattering, revealing a flexible yet stable interaction. This pathway can be adapted and utilized to study various viral and human long-non-coding RNA–RNA interactions and determine their binding affinities, a critical pharmacological property of designing potential therapeutics.

The social needs of rural families facing cancer warrant investigation to inform psychosocial care planning and policy development.Using purposive sampling, we interviewed 24 rural caregivers and 17 hospital staff from an academic cancer center in the U.S. South. Social needs were defined as the support needed to effectively provide informal caregiving across economic, physical, interpersonal, and service domains. We used the framework method to code and synthesize findings.Caregiver economic and physical needs were interconnected and most pressing, including common examples of distance to care and transportation barriers. Caregivers desired additional support from the health system, insurance providers, and community resources. Staff identified similar need patterns and gaps in health system capacity.Rural cancer caregivers experience multiple unmet social needs. Supportive interventions for this population will benefit from flexible implementation and multilevel, multisector approaches. In particular, interventions that address financial hardship and limited internet access are needed.

To determine factors associated with restarting therapeutic antibiotics within 30 days of head and neck microvascular free tissue transfer (HN-MFTT).Retrospective study of consecutive HN-MFTTs performed from January 2015 to July 2020.Tertiary academic medical center.Thirty-day postoperative antibiotic use and post-HN-MFTT surgical and medical complications were assessed. Univariable analyses and multivariable logistic regression were used to evaluate risk factors associated with restarting antibiotics.overall 482 patients with 501 HN-MFTTs were stratified by duration of prophylaxis: ≤24 hours (n = 136, 27.1%), 25-72 hours (n = 54, 10.8%), and72 hours (n = 311, 62.1%). Antibiotics were restarted in 199 patients (209 procedures, 42%). The most common indications for antibiotic reinitiation were flap recipient site infection (n = 59, 28%); hospital-acquired pneumonia (n = 44, 21%); and wound dehiscence, fluctuance, or change in quality of drain output (n = 44, 21%). Shorter antibiotic prophylaxis (≤24 hours) (odds ratio [OR], 1.95; 95% CI, 1.2-3.0;Aerodigestive reconstruction, 24-hour postoperative antimicrobial prophylaxis, American Society of Anesthesiologists class 3 and 4, prior chemotherapy/immunotherapy, cardiovascular disease, and osteocutaneous flaps are associated with reinitiation of antibiotics within 30 days of HN-MFTT.

Background: Infection with hepatitis C virus (HCV) is associated with an increased risk of developing head and neck cancer (HNC), and negatively impacts cancer-specific survival. Objective: To meas...

Background: Anterolateral thigh (ALT) microvascular free tissue transfer is an integral part of head and neck reconstructive surgery, but it can be complicated by postoperative donor site fluid col...

Funding Acknowledgements Type of funding sources: None. Background Apical hypertrophic cardiomyopathy (HCM) is considered to have a benign prognosis in terms of cardiovascular mortality. Sudden cardiac arrest and ventricular fibrillation (VF) in patients with apical HCM is rarely reported. Methods Between July 2001 and May 2021, 96 HCM patients who had undergone implantable cardioverter-defibrillator (ICD) implantation from three tertiary hospitals were reviewed. We evaluated the prevalence of aborted sudden cardiac death and/or documented VF in apical HCM and known risk markers for sudden cardiac death in those populations. Result Fifteen patients (15.6%) were apical HCM in total population. Among apical HCM, seven patients (40.0%) presented with aborted sudden cardiac death or documented VF, therefore received ICD implantation for the secondary prevention. All seven patients had at least one risk marker suggested either 2020 ACC/AHA guideline or 2014 ESC guideline. One patient had three risk factors and two patients had two risk factors and four patients had one risk factor. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), personal history of unexplained syncope and non-sustained ventricular tachycardia (VT) were the common risk factors. Conclusions Clinical outcomes in patients with apical HCM are not always as benign as previously thought. ICD implantation should be considered in high-risk patients with apical HCM as the same manner with the septal type of HCM according to the current guideline recommendations.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Korean Society of Cardiology Background Anticoagulation with warfarin in Korean patients with atrial fibrillation (AF) often has been decreased as an international normalized ratio (INR) of prothrombin time between 1.6 to 2.6 for the fear of bleeding, although universal criteria recommends to adjust it between 2.0 to 3.0. Methods In this randomized, open-label trial, we compared low intensity anticoagulation (INR 1.6 to 2.6) with standard intensity anticoagulation (INR 2.0 to 3.0) with warfarin in 616 patients with AF and at least 1 risk factor for stroke. The per-protocol, intension-to-treatment analysis was designed to determine whether low-intensity anticoagulation (n=308) was non-inferior to standard-intensity anticoagulation (n=308) with warfarin for the primary end point of net clinical outcomes defined as the sum of stroke, systemic embolism, major bleeding and death. Results The median follow-up duration was 1.8 years. Baseline characteristics of the two groups were comparable. Median value of INR was significantly higher in standard-intensity group than low-intensity group (2.19 vs. 2.07, p=0.002), whereas that of time in the therapeutic range was comparable between the 2 groups. The rate of primary outcome was 1.55% per year in low-intensity anticoagulation, as compared with 2.46% per year in standard-intensity anticoagulation (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.22 to 1.74, p for non-inferiority Conclusion In Korean patients with AF, low-intensity anticoagulation with warfarin as INR 1.6 to 2.6 was non-inferior to standard-intensity anticoagulation with warfarin as INR 2.0 to 3.0 for the prevention of net-clinical outcome, and stroke or systemic embolism. There was no significant difference for the risk reduction of major bleeding.

Median arcuate ligament syndrome is a rare disease with overlapping symptoms of broad foregut pathology. Appropriately selected patients can benefit from a laparoscopic or open median arcuate ligament release. Institutional series have reported the outcomes of open and laparoscopic techniques but there are no nationwide analysis comparing both techniques and overall trends in treatment.Cross-sectional study using the American College of Surgeons-National Surgical Quality Improvement Project from 2010 to 2020. Celiac artery compression syndrome cases were identified by International Classification of Diseases (ICD) codes and categorized as open or laparoscopic. Trends in the use of each technique and 30-day complications were compared between the groups.A total of 578 open cases (76%) and 185 laparoscopic cases (24%) were identified. There was an increase adoption of the laparoscopic approach, with 22% of the cases employing this technique at the end of the study period, compared to 7% at the beginning of the study period. The open group had a higher prevalence of hypertension (26% vs 18%, p = 0.04) and bleeding disorders (5% vs 2%, p 0.03). Laparoscopic approach had a shorter length of stay (2.3 days vs 5.2 days, p 0.0001), lower major complication rates (0.5% vs 4.0%, p = 0.02) and lower reoperation rates (0% vs 2.6%, p = 0.03). Overall mortality was 0.1%.Overall numbers of surgical intervention for treatment of median arcuate ligament increased during this timeframe, as well as increased utilization of the laparoscopic approach. It appears to be an overall safe procedure, offering lower rates of complications and shorter length of stay.

Although parents with cancer report that talking with their children about cancer and dying is distressing, accessible support is rare. We assessed the feasibility, acceptability, and preliminary effects of Families Addressing Cancer Together (FACT), a web-based, tailored psychosocial intervention to help parents talk about their cancer with their children.This pilot study used a pre-posttest design. Eligible participants were parents with new or metastatic solid tumors who had minor (ages 3-18) children. Participants who completed baseline assessments received online access to FACT. We assessed feasibility through enrollment and retention rates and reasons for study refusal. Acceptability was evaluated by satisfaction ratings. We examined participants' selection of intervention content and preliminary effects on communication self-efficacy and other psychosocial outcomes (depression and anxiety symptoms, health-related quality of life, family functioning) at 2- and 12-week post-intervention.Of 68 parents we approached, 53 (78%) agreed to participate. Forty-six parents completed baseline assessments and received the FACT intervention. Of the 46 participants, 35 (76%) completed 2-week assessments, and 25 (54%) completed 12-week assessments. Parents reported that FACT was helpful (90%), relevant (95%), and easy to understand (100%). Parents' psychosocial outcomes did not significantly improve post-intervention, but parents endorsed less worry about talking with their child (46% vs. 37%) and reductions in the number of communication concerns (3.4 to 1.8).The FACT intervention was feasible, acceptable, and has potential to address communication concerns of parents with cancer. A randomized trial is needed to test its efficacy in improving psychological and parenting outcomes.This study was IRB-approved and registered with clinicaltrials.gov (NCT04342871).

This study's purpose was to determine if ondansetron can prevent pruritus after administration of intrathecal morphine in children, as has been demonstrated in adults.A double-blinded, randomized placebo-controlled trial.Operating room and first 24 h postoperative inpatient stay at an academic children's hospital.Forty-six children aged 3-17 years, who received 4-5 mcg/kg intrathecal morphine for urological or orthopedic procedures were included.Children were randomized to receive intravenous ondansetron (treatment) or saline placebo (placebo), prior to intrathecal morphine administration, and q6H for 24 h thereafter. Intraoperative anti-emetics and postoperative rescue treatments for pruritus and nausea were standardized.Patients were interviewed q6H for scored pruritus, nausea, and pain, using standardized scales.The trial was terminated for futility after interim analysis. Forty-six children were recruited and 45 completed data collection. No significant difference was found between both groups for incidence of pruritus (requiring treatment) [relative risk (RR) 0.9, 95% CI: 0.7, 1.2], during the first postoperative 24 h. Notably, the incidence of pruritus was 84% overall, much higher than rates in previously published studies. Intravenous ondansetron significantly reduced the incidence of nausea, compared with the placebo group [RR 0.5, 95% CI: 0.3, 0.9].This study found no evidence for intravenous ondansetron as an effective preventative for pruritus following intrathecal morphine in children. However, this RCT did find that the rate of pruritus following intrathecal morphine administration may be significantly higher than previously thought. Nausea and vomiting (a secondary outcome) were reduced significantly in the treatment group. The negative findings of this study reinforce the potential dangers of extrapolating the drug effects seen in adults onto pediatric patients.

Remarkable advances have been made in schizophrenia (SCZ) GWAS, but gleaning biological insight from these loci is challenging. Genetic influences on gene expression (e.g., eQTLs) are cell type-specific, but most studies that attempt to clarify GWAS loci's influence on gene expression have employed tissues with mixed cell compositions that can obscure cell-specific effects. Furthermore, enriched SCZ heritability in the fetal brain underscores the need to study the impact of SCZ risk loci in specific developing neurons. MGE-derived cortical interneurons (cINs) are consistently affected in SCZ brains and show enriched SCZ heritability in human fetal brains. We identified SCZ GWAS risk genes that are dysregulated in iPSC-derived homogeneous populations of developing SCZ cINs. These SCZ GWAS loci differential expression (DE) genes converge on the PKC pathway. Their disruption results in PKC hyperactivity in developing cINs, leading to arborization deficits. We show that the fine-mapped GWAS locus in the ATP2A2 gene of the PKC pathway harbors enhancer marks by ATACseq and ChIPseq, and regulates ATP2A2 expression. We also generated developing glutamatergic neurons (GNs), another population with enriched SCZ heritability, and confirmed their functionality after transplantation into the mouse brain. Then, we identified SCZ GWAS risk genes that are dysregulated in developing SCZ GNs. GN-specific SCZ GWAS loci DE genes converge on the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca

In this study, homogeneous calcareous deposit films were formed via electrodeposition, and the characteristics of the films were studied using various surface analytical techniques. In addition, the optimal conditions were determined, and the anti-corrosive effect was confirmed via electrodeposition to form uniform and compact aragonite films in marine environments such as submerged and tidal zones. The calcareous deposit films formed in the tidal zone were thinner compared to those formed in the submerged zone. However, the aragonite–CaCO3 ratio in the tidal zone was high and the films were firm and dense. The adhesion properties were excellent at 3 and 1 A/m2, and the current density was reduced by more than 90% because the films were formed on the steel surface.