The importance of highlighting the role of the self in hypnotherapy and hypnosis.

The role of the patient in hypnotherapy can be underestimated by both the therapist and the patient. This is likely due to the focus the hypnosis literature has had on the role played by the hypnotist/therapist and less on the phenomenological control (control over subjective experience) applied by the patient. Whilst early approaches to hypnosis and hypnotherapy included concepts such as autosuggestion and self-hypnosis, the role of the self has been largely overlooked. Here we aim to highlight the importance of the self in hypnotherapy and hypnosis by considering the concept of self-hypnosis and how it relates to hetero-hypnosis. We will show that: 1) historically the self was an important component of the concept of hypnosis; 2) extant theories emphasise the role of the self in hypnosis; 3) self-hypnosis is largely indistinguishable from hetero-hypnosis; 4) self-hypnosis is as effective as hetero-hypnosis. We also argue that highlighting the role of the self in hypnotherapy and hypnosis could increase feelings of self-efficacy, especially given that it can be considered a skill that can be advanced and implies self-control and not "mind-control". Highlighting the role of phenomenological control by the patient could also increase the uptake of hypnotherapy as treatment for various disorders.

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma.

Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma. Plasma membrane-enriched mass spectrometry identified 1,461 cell surface proteins in cell lines and 1,401 in xenograft models, respectively. Additional proteogenomic analyses revealed 60 high-confidence candidate immunotherapeutic targets and we prioritized Delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlated with the presence of a super-enhancer spanning the DLK1 locus. Robust cell surface expression of DLK1 was validated by immunofluorescence, flow cytometry, and immunohistochemistry. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells resulted in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), showed potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Moreover, DLK1 is highly expressed in several adult cancer types, including adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PCPG), hepatoblastoma, and small cell lung cancer (SCLC), suggesting potential clinical benefit beyond neuroblastoma. Taken together, our study demonstrates the utility of comprehensive cancer surfaceome characterization and credentials DLK1 as an immunotherapeutic target. Highlights: Plasma membrane enriched proteomics defines surfaceome of neuroblastomaMulti-omic data integration prioritizes DLK1 as a candidate immunotherapeutic target in neuroblastoma and other cancersDLK1 expression is driven by a super-enhancer DLK1 silencing in neuroblastoma cells results in cellular differentiation ADCT-701, a DLK1-targeting antibody-drug conjugate, shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma preclinical models.

KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas.

Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find KCNQ family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions. This also highlights novel roles of KCNQ3 in non-excitable tissues. We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors.

Marine picocyanobacterial PhnD1 shows specificity for various phosphorus sources but likely represents a constitutive inorganic phosphate transporter.

Despite being fundamental to multiple biological processes, phosphorus (P) availability in marine environments is often growth-limiting, with generally low surface concentrations. Picocyanobacteria strains encode a putative ABC-type phosphite/phosphate/phosphonate transporter, phnDCE, thought to provide access to an alternative phosphorus pool. This, however, is paradoxical given most picocyanobacterial strains lack known phosphite degradation or carbon-phosphate lyase pathway to utilise alternate phosphorus pools. To understand the function of the PhnDCE transport system and its ecological consequences, we characterised the PhnD1 binding proteins from four distinct marine Synechococcus isolates (CC9311, CC9605, MITS9220, and WH8102). We show the Synechococcus PhnD1 proteins selectively bind phosphorus compounds with a stronger affinity for phosphite than for phosphate or methyl phosphonate. However, based on our comprehensive ligand screening and growth experiments showing Synechococcus strains WH8102 and MITS9220 cannot utilise phosphite or methylphosphonate as a sole phosphorus source, we hypothesise that the picocyanobacterial PhnDCE transporter is a constitutively expressed, medium-affinity phosphate transporter, and the measured affinity of PhnD1 to phosphite or methyl phosphonate is fortuitous. Our MITS9220_PhnD1 structure explains the comparatively lower affinity of picocyanobacterial PhnD1 for phosphate, resulting from a more limited H-bond network. We propose two possible physiological roles for PhnD1. First, it could function in phospholipid recycling, working together with the predicted phospholipase, TesA, and alkaline phosphatase. Second, by having multiple transporters for P (PhnDCE and Pst), picocyanobacteria could balance the need for rapid transport during transient episodes of higher P availability in the environment, with the need for efficient P utilisation in typical phosphate-deplete conditions.

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial.

PURPOSE: To determine the safety and toxicity profile of intravitreal carboplatin as salvage treatment for retinoblastoma with vitreous disease. DESIGN: Single-institution, interventional prospective clinical trial. PARTICIPANTS: Patients with progressive or recurrent vitreous seeds after completion of primary treatment for intraocular retinoblastoma. METHODS: Eligible eyes received an intravitreal injection of carboplatin every 14 to 21 days with simultaneous focal therapy (laser, thermotherapy, and brachytherapy) provided at the discretion of the ocular oncologist. The evaluation with examination under anesthesia, ultrasound biomicroscopy, and electroretinography (ERG) were performed before each injection to assess for tumor response and drug-related toxicity. A serious adverse event resulted in dose recalculation and ultimately early closure of the study. MAIN OUTCOME MEASURES: Regression pattern of vitreous disease and incidence of dose-limiting toxicities. RESULTS: Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients after 5, 2, 2, and 1 injections (respectively). Two patients developed recurrent vitreous disease at 3 and 25 months after complete regression and ultimately required enucleation. A serious adverse event occurred in 1 patient who developed acute vision loss with extinguished ERG response 72 hours after the second injection; ultimately, this eye developed a cataract and required enucleation. After temporary suspension and dose modification, 3 patients were enrolled at an injection dose of 3 µg and treated with a total of 5, 2, and 1 injections, respectively. Complete regression of vitreous disease was not achieved in any patient though ERG amplitudes remained stable. After removal from protocol, all 3 patients had a complete response to intravitreal melphalan. Concern for dose escalation and further toxicity in the setting of an effective and safe alternative (melphalan) led to the termination of the study. CONCLUSIONS: Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses, but permanent retinal toxicity was observed. Other alternative agents should be considered. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Antioxidants from Hyeronima macrocarpa Berries Loaded on Nanocellulose: Thermal and Antioxidant Stability.

This study investigated the effect of different storage temperatures (35-55 °C) on the bioactive substances and antioxidant properties of Hyeronima macrocarpa berries loaded on nanocellulose. NC was extracted from banana pseudo-stems and presented an interesting surface and porosity properties. The acidified ethanol extract showed better anthocyanin extraction (1317 mg C3G eq./100 g FW) and was used for the preparation of the powdered product, which presented an intense and uniform magenta color, with CIELAB parameters of L* = 59.16, a* = 35.61, and b* = 7.08. The powder exhibited significant stability at storage temperatures of 35 and 45 °C, in which there was no significant loss of anthocyanins or a decrease in antioxidant capacity. In addition, the color was stable for up to 4 months without adding any preservative agent. The anthocyanin-rich extract of H. macrocarpa reached an estimated shelf-life of 315 days (stored at 35 °C), as a result of the impregnation process between the extract and NC, with the ability to protect the bioactives from degradation, due to NC surface properties.

Concreteness and levels of processing: a test of the dual-coding hypothesis using dynamic visual noise.

Concreteness and levels of processing (LOP) effects have been attributed to the differential availability of visual images for concrete words, and at deeper levels of processing, respectively. Interestingly, the concreteness effect has been shown to disappear under conditions involving dynamic visual noise (DVN), which is thought to suppress the generation of visual images from long-term memory. The present study further investigated the role of visual imagery in concreteness and LOP effects. Across four experiments, DVN was manipulated during study, and participants' memory for concrete and abstract words was measured using recall and recognition tests. Although some support for dual-coding was found, concreteness and LOP effects were not fully explained by visual imagery because they were present under DVN conditions. We conclude that concreteness and LOP effects may be better explained by an "extended dual-coding theory" that incorporates the role of context availability in accounting for this pattern of results.

Economic estimation of Bitcoin mining's climate damages demonstrates closer resemblance to digital crude than digital gold.

This paper provides economic estimates of the energy-related climate damages of mining Bitcoin (BTC), the dominant proof-of-work cryptocurrency. We provide three sustainability criteria for signaling when the climate damages may be unsustainable. BTC mining fails all three. We find that for 2016-2021: (i) per coin climate damages from BTC were increasing, rather than decreasing with industry maturation; (ii) during certain time periods, BTC climate damages exceed the price of each coin created; (iii) on average, each $1 in BTC market value created was responsible for $0.35 in global climate damages, which as a share of market value is in the range between beef production and crude oil burned as gasoline, and an order-of-magnitude higher than wind and solar power. Taken together, these results represent a set of sustainability red flags. While proponents have offered BTC as representing "digital gold," from a climate damages perspective it operates more like "digital crude".

The Impact of Nurses' Beliefs, Attitudes, and Cultural Sensitivity on the Management of Patient Pain.

INTRODUCTION: Nurses' attitudes and beliefs may impact pain management. This study investigated nurses' perceptions regarding their own and patients' pain experiences by examining relationships between pain cautiousness and stoicism, cultural sensitivity, and personal pain attitudes. METHODOLOGY: A correlational methodology examined nursing staff in a Midwestern private hospital. The sample included 102 primarily female (95.1%), Caucasian (97%), and married (66%) nursing staff. Measures included the Intercultural Sensitivity Scale, Pain Attitudes Questionnaire to Assess Stoicism and Cautiousness, and the Pain Management: Nurses' Knowledge and Attitude Survey. RESULTS: Cultural sensitivity was a significant predictor of pain knowledge and attitudes total score (R2 = .081, ß = .244, p = .040), while pain stoicism and pain cautiousness were not predictive. DISCUSSION: Findings highlight the importance of nurses being aware of personal attitudes, beliefs, and cultural sensitivity in pain management. Results also demonstrate a gap between the knowledge and utilization of nonpharmacologic pain management interventions among nursing staff.

Thirty-Two Weeks of Oral Supplementation with LinPro™ Increases Hoof Growth in Healthy Mares.

LinPro™ (LP) is a commercial dietary supplement marketed to increase hoof growth and quality. Ten mature (5-15 years) non-pregnant Quarter Horse mares without existing hoof quality issues were used to test the hypothesis that 32 weeks of daily supplementation with 113 g of LP would increase hoof growth rates as compared to non-supplemented controls. Hooves were trimmed at the start of the study and every 8 weeks thereafter. A mark was applied on the hoof wall surface at 2.5 cm below the junction of the hoof wall and coronary band. At each trimming, the distance between the mark and coronary band was measured and a new mark placed. For front hooves, horses assigned to LP had greater total hoof growth over 32 weeks (2.65 ± 0.15 vs. 2.18 ± 0.12 cm; P = .048) and tended to have greater hoof growth per 8 weeks trimming cycle (0.64 ± 0.03 vs. 0.55 ± 0.03 cm; P = .085) than horses assigned to non-supplemented controls (CON). Horses assigned to LP had greater plasma biotin concentrations (2158 ± 69 vs. 636 ± 62 ng/L; P < .001) and proportions of erucic acid in hoof tissue (1.03 ± 0.08 vs. 0.76 ± 0.07 %; P = .049) as compared to CON. Further, the most abundant fatty acids in hoof tissue were stearic, palmitic, oleic, and linoleic acids. LinPro may provide an effective treatment to improve hoof growth rates in horses with otherwise healthy hooves.

Developing an algorithm across integrated healthcare systems to identify a history of cancer using electronic medical records.

OBJECTIVE: Tumor registries in integrated healthcare systems (IHCS) have high precision for identifying incident cancer but often miss recently diagnosed cancers or those diagnosed outside of the IHCS. We developed an algorithm using the electronic medical record (EMR) to identify people with a history of cancer not captured in the tumor registry to identify adults, aged 40-65 years, with no history of cancer. MATERIALS AND METHODS: The algorithm was developed at Kaiser Permanente Colorado, and then applied to 7 other IHCS. We included tumor registry data, diagnosis and procedure codes, chemotherapy files, oncology encounters, and revenue data to develop the algorithm. Each IHCS adapted the algorithm to their EMR data and calculated sensitivity and specificity to evaluate the algorithm's performance after iterative chart review. RESULTS: We included data from over 1.26 million eligible people across 8 IHCS; 55 601 (4.4%) were in a tumor registry, and 44848 (3.5%) had a reported cancer not captured in a registry. The common attributes of the final algorithm at each site were diagnosis and procedure codes. The sensitivity of the algorithm at each IHCS was 90.65%-100%, and the specificity was 87.91%-100%. DISCUSSION: Relying only on tumor registry data would miss nearly half of the identified cancers. Our algorithm was robust and required only minor modifications to adapt to other EMR systems. CONCLUSION: This algorithm can identify cancer cases regardless of when the diagnosis occurred and may be useful for a variety of research applications or quality improvement projects around cancer care.

Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tumors with IDH mutations. Using genetic and pharmacological approaches, we demonstrated that glutaminase-mediated glutamine metabolism played distinct roles in enchondromas and chondrosarcomas with IDH1 or IDH2 mutations. Glutamine affected cell differentiation and viability in these tumors differently through different downstream metabolites. During murine enchondroma-like lesion development, glutamine-derived α-ketoglutarate promoted hypertrophic chondrocyte differentiation and regulated chondrocyte proliferation. Deletion of glutaminase in chondrocytes with Idh1 mutation increased the number and size of enchondroma-like lesions. In contrast, pharmacological inhibition of glutaminase in chondrosarcoma xenografts reduced overall tumor burden partially because glutamine-derived non-essential amino acids played an important role in preventing cell apoptosis. This study demonstrates that glutamine metabolism plays different roles in tumor initiation and cancer maintenance. Supplementation of α-ketoglutarate and inhibiting GLS may provide a therapeutic approach to suppress enchondroma and chondrosarcoma tumor growth, respectively. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a patient is found to have American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III or IV melanoma (i.e., any metastatic spread beyond the primary tumour) and that patient's BRAF mutation status is hitherto unknown, even if BRAF mutation testing has not been specifically requested by the treating clinician (in Australia, Medicare-subsidised BRAFV600 mutation testing does not need to be requested by the treating clinician). When performed in centres with appropriate expertise and experience, immunohistochemistry (IHC) using the anti-BRAF V600E monoclonal antibody (VE1) can be a highly sensitive and specific means of detecting BRAFV600E mutations, and may be used as a rapid and relatively inexpensive initial screening test. However, VE1 immunostaining can be technically challenging and difficult to interpret, particularly in heavily pigmented tumours; melanomas with weak, moderate or focal BRAFV600E immunostaining should be regarded as equivocal. It must also be remembered that other activating BRAFV600 mutations (including BRAFV600K), which account for ∼10-20% of BRAFV600 mutations, are not detected with currently available IHC antibodies. For these reasons, if available and practicable, we recommend that DNA-based BRAF mutation testing always be performed, regardless of whether IHC-based testing is also conducted. Advice about tissue/specimen selection for BRAF mutation testing of patients diagnosed with stage III or IV melanoma is also offered in this article; and potential pitfalls when interpreting BRAF mutation tests are highlighted.

Selenium abates manganese-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats.

Excessive exposure to manganese (Mn) is associated with neurotoxicity characterized by oxidative stress, inflammation, and apoptosis induction. Selenium (Se) has been shown to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in humans and animals. The present study investigated the neuroprotective mechanism of Se in rats sub-chronically treated with Mn at 30 mg/kg body weight or orally co-treated with Se at 0.2 and 0.4 mg/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were recorded and computed with the aid of ANY-Maze (a video-tracking software) for 5-min trial, in a novel apparatus. The ANY-Maze analysis showed that Se significantly (p < 0.05) abated Mn-induced locomotive impairment evidenced by increased in maximum speed, total time traveled, absolute turn angle, number of line crossing, rotation and forelimb grip and decreased total time immobile, grooming, and negative geotaxis as verified by the enhanced track plot density. Furthermore, the striatum and hippocampus of the rats were excised and the levels of Mn and Se, oxidative stress markers, proinflammatory cytokines including acetylcholinesterase and caspase-3 activities were assayed. The result shows that Se abates Mn-mediated accumulation of Mn. Also, Se ameliorated Mn-induced decrease in antioxidant enzymes as well as glutathione level and increase in acetylcholinesterase activity, lipid peroxidation, proinflammatory cytokines (i.e., interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha), and caspase-3 activation in the striatum and hippocampus of the rats. Collectively, Se abated Mn-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Se may serve as a neuroprotective agent against Mn-mediated neurotoxicity.

Shared Decision Making in Cardiac Electrophysiology Procedures and Arrhythmia Management.

Shared decision making (SDM) has been advocated to improve patient care, patient decision acceptance, patient-provider communication, patient motivation, adherence, and patient reported outcomes. Documentation of SDM is endorsed in several society guidelines and is a condition of reimbursement for selected cardiovascular and cardiac arrhythmia procedures. However, many clinicians argue that SDM already occurs with clinical encounter discussions or the process of obtaining informed consent and note the additional imposed workload of using and documenting decision aids without validated tools or evidence that they improve clinical outcomes. In reality, SDM is a process and can be done without decision tools, although the process may be variable. Also, SDM advocates counter that the low-risk process of SDM need not be held to the high bar of demonstrating clinical benefit and that increasing the quality of decision making should be sufficient. Our review leverages a multidisciplinary group of experts in cardiology, cardiac electrophysiology, epidemiology, and SDM, as well as a patient advocate. Our goal is to examine and assess SDM methodology, tools, and available evidence on outcomes in patients with heart rhythm disorders to help determine the value of SDM, assess its possible impact on electrophysiological procedures and cardiac arrhythmia management, better inform regulatory requirements, and identify gaps in knowledge and future needs.

Functional characterisation of substrate-binding proteins to address nutrient uptake in marine picocyanobacteria.

Marine cyanobacteria are key primary producers, contributing significantly to the microbial food web and biogeochemical cycles by releasing and importing many essential nutrients cycled through the environment. A subgroup of these, the picocyanobacteria (Synechococcus and Prochlorococcus), have colonised almost all marine ecosystems, covering a range of distinct light and temperature conditions, and nutrient profiles. The intra-clade diversities displayed by this monophyletic branch of cyanobacteria is indicative of their success across a broad range of environments. Part of this diversity is due to nutrient acquisition mechanisms, such as the use of high-affinity ATP-binding cassette (ABC) transporters to competitively acquire nutrients, particularly in oligotrophic (nutrient scarce) marine environments. The specificity of nutrient uptake in ABC transporters is primarily determined by the peripheral substrate-binding protein (SBP), a receptor protein that mediates ligand recognition and initiates translocation into the cell. The recent availability of large numbers of sequenced picocyanobacterial genomes indicates both Synechococcus and Prochlorococcus apportion >50% of their transport capacity to ABC transport systems. However, the low degree of sequence homology among the SBP family limits the reliability of functional assignments using sequence annotation and prediction tools. This review highlights the use of known SBP structural representatives for the uptake of key nutrient classes by cyanobacteria to compare with predicted SBP functionalities within sequenced marine picocyanobacteria genomes. This review shows the broad range of conserved biochemical functions of picocyanobacteria and the range of novel and hypothetical ABC transport systems that require further functional characterisation.

Rapid genetic screening with high quality factor metasurfaces.

Genetic analysis methods are foundational to advancing personalized and preventative medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and DNA microarrays rely on fluorescence and absorbance, necessitating sample amplification or replication and leading to increased processing time and cost. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with monolayers of nucleic acid fragments. Each nanoantenna exhibits substantial electromagnetic field enhancements with sufficiently localized fields to ensure isolation from neighboring resonators, enabling dense biosensor integration. We quantitatively detect complementary target sequences using DNA hybridization simultaneously for arrays of sensing elements patterned at densities of 160,000 pixels per cm$^2$. In physiological buffer, our nanoantennas exhibit average resonant quality factors of 2,200, allowing detection of two gene fragments, SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b), down to femtomolar concentrations. We also demonstrate high specificity sensing in clinical nasopharyngeal eluates within 5 minutes of sample introduction. Combined with advances in biomarker isolation from complex samples (e.g., mucus, blood, wastewater), our work provides a foundation for rapid, compact, amplification-free and high throughput multiplexed genetic screening assays spanning medical diagnostics to environmental monitoring.