Langerhans cells regulate immunity in adulthood by regulating postnatal dermal lymphatic development.

The communication between skin and draining lymph nodes is crucial for well-regulated immune responses to skin insults. The skin sends antigen and other signals via lymphatic vessels to regulate lymph node activity, and regulating dermal lymphatic function is another means to control immunity. Here, we show that Langerhans cells (LCs), epidermis-derived antigen-presenting cells, mediate dermal lymphatic expansion and phenotype acquisition postnatally, a function is independent of LC entry into lymphatic vessels. This postnatal LC-lymphatic axis serves in part to control inflammatory systemic T cell responses in adulthood. Our data provide a tissue-based mechanism by which LCs regulate T cells remotely across time and space and raise the possibility that immune diseases in adulthood could reflect compromise of the LC-lymphatic axis in childhood.

Coping with stress: Salt type, concentration, and exposure history limit life history tradeoffs in response to road salt salinization.

Substantial increases in the salinity of freshwater ecosystems has occurred around the globe from causes such as climate change, industrial operations, and the application of road deicing salts. We know very little about how plastic responses in life history traits or rapid evolution of new traits among freshwater organisms could promote stability in ecological communities affected by salinization. We performed a cohort life history analysis from birth to death with 180 individuals of a ubiquitous freshwater zooplankter to understand how life history traits are affected by exposure to two common salt types causing salinization-sodium chloride (NaCl) and calcium chloride (CaCl2)-across two environmentally relevant concentrations. We also tested if a multi-generational exposure history to high salinity altered life-history responses. We tracked and measured lifespan, time to maturation, brood size, brood interval, and body size. We found smaller brood sizes but slightly longer lifespans occurred at a low concentration of NaCl (230 mg Cl-/L). The longer lifespans led to more, albeit smaller broods, which generated a similar lifetime reproductive output compared to the no-salt control populations. At higher concentrations of NaCl and CaCl2, we found lifetime reproductive output was reduced by 23 % to 83 % relative to control populations because no tradeoff among life history traits occurred. In CaCl2, we observed shorter life spans, longer time intervals between smaller broods, and smaller body sizes leading to reduced lifetime reproductive output. We also found that a multi-generational exposure to the salt types did not convey any advantages for lifetime reproductive output. In some cases, the exposure history worsened the life history trait responses suggesting maladaptation. Our findings suggest that life history tradeoffs for freshwater species can occur in response to salinization, but these tradeoffs will largely depend on salt type and concentration, which will have implications for biodiversity and ecological stability.

Trafficking of adhesion and aggregation-modulating proteins during the early stages of Dictyostelium development.

The social amoeba Dictyostelium discoideum has been studied for close to a century to better understand conserved cellular and developmental processes. The life cycle of this model eukaryote is composed of a unicellular growth phase and a multicellular developmental phase that is induced by starvation. When starved, individual cells undergo chemotactic aggregation to form multicellular mounds that develop into slugs. Terminal differentiation of cells within slugs forms fruiting bodies, each composed of a stalk that supports a mass of viable spores that germinate and restart the life cycle when nutrients become available. Calcium-dependent cell adhesion protein A (CadA) and countin (CtnA) are two proteins that regulate adhesion and aggregation, respectively, during the early stages of D. discoideum development. While the functions of these proteins have been well-studied, the mechanisms regulating their trafficking are not fully understood. In this study, we reveal pathways and cellular components that regulate the intracellular and extracellular amounts of CadA and CtnA during aggregation. During growth and starvation, CtnA localizes to cytoplasmic vesicles and punctae. We show that CtnA is glycosylated and this post-translational modification is required for its secretion. Upon autophagy induction, a signal peptide for secretion facilitates the release of CtnA from cells via a pathway involving the µ subunit of the AP3 complex (Apm3) and the WASP and SCAR homolog, WshA. Additionally, CtnA secretion is negatively regulated by the D. discoideum orthologs of the human non-selective cation channel mucolipin-1 (Mcln) and sorting receptor sortilin (Sort1). As for CadA, it localizes to the cell periphery in growth-phase and starved cells. The intracellular and extracellular amounts of CadA are modulated by autophagy genes (atg1, atg9), Apm3, WshA, and Mcln. We integrate these data with previously published findings to generate a comprehensive model summarizing the trafficking of CadA and CtnA in D. discoideum. Overall, this study enhances our understanding of protein trafficking during D. discoideum aggregation, and more broadly, provides insight into the multiple pathways that regulate protein trafficking and secretion in all eukaryotes.

Reactivity of Tetrel-Functionalized Heptaphosphane Clusters toward Azides.

In this work, the reactivity of tetrel-functionalized phosphorus clusters toward organoazides is probed. Clusters (Me3Si)3P7 (1) and (Me3Ge)3P7 (2) were reacted with benzyl azide, phenyl azide, and 4-bromophenyl azide, and it was found that the [RN] (R = benzyl, phenyl, and 4-bromophenyl) unit from the azide inserted into the phosphorus-tetrel bonds on the cluster, accompanied by N2 elimination. Through control of the azide stoichiometry, the mono-, bis-, and tris-inserted products could be observed, consistent with these insertions proceeding in a stepwise manner. The bonding between the amine moieties and clusters was further investigated by computational chemistry, and the findings were consistent with the phosphorus cluster having undergone a formal oxidation. These insertion reactions are a convenient means of accessing Zintl clusters functionalized with exo-nitrogen-bonded moieties, which, to the best of our knowledge, were previously unknown.

Assaying Lysosomal Enzyme Activity in Dictyostelium discoideum.

Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules including nucleic acids, proteins, polysaccharides, and lipids. In addition to functioning within lysosomes, lysosomal enzymes are also secreted. Alterations in the levels and activities of lysosomal enzymes dysregulates lysosomes, which can lead to the intralysosomal accumulation of biological material and the development of lysosomal storage diseases (LSDs) in humans. Dictyostelium discoideum has a long history of being used to study the trafficking and functions of lysosomal enzymes. More recently, it has been used as a model system to study several LSDs. In this chapter, we outline the methods for assessing the activity of several lysosomal enzymes in D. discoideum (α-galactosidase, ß-galactosidase, α-glucosidase, ß-glucosidase, ß-N-acetylglucosaminidase, α-mannosidase, cathepsin B, cathepsin D, cathepsin F, palmitoyl protein thioesterase 1, and tripeptidyl peptidase 1).

Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors.

PURPOSE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts. METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208). RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.

Crystalline Antimony Selenide Thin Films for Optoelectronics through Photonic Curing.

Thermal annealing is the most common postdeposition technique used to crystallize antimony selenide (Sb2Se3) thin films. However, due to slow processing speeds and a high energy cost, it is incompatible with the upscaling and commercialization of Sb2Se3 for future photovoltaics. Herein, for the first time, a fast-annealing technique that uses millisecond light pulses to deliver energy to the sample is adapted to cure thermally evaporated Sb2Se3 films. This study demonstrates how photonic curing (PC) conditions affect the outcome of Sb2Se3 phase conversion from amorphous to crystalline by evaluating the films' crystalline, morphological, and optical properties. We show that Sb2Se3 is readily converted under a variety of different conditions, but the zone where suitable films for optoelectronic applications are obtained is a small region of the parameter space. Sb2Se3 annealing with short pulses (<3 ms) shows significant damage to the sample, while using longer pulses (>5 ms) and a 4-5 J cm-2 radiant energy produces (211)- and (221)-oriented crystalline Sb2Se3 with minimal to no damage to the sample. A proof-of-concept photonically cured Sb2Se3 photovoltaic device is demonstrated. PC is a promising annealing method for large-area, high-throughput annealing of Sb2Se3 with various potential applications in Sb2Se3 photovoltaics.

Right anterior mini thoracotomy for redo cardiac surgery: case series from North America and Europe.

Background: Right anterior mini thoracotomy (RAMT) for aortic valve replacement (AVR) is a minimally invasive procedure that avoids sternotomy. Herein, we report the outcomes of patients who underwent redo-cardiac via a RAMT approach for AVR. Methods: This case series reports the clinical outcomes of 14 consecutive redo operations, done in Calgary (Canada) and Gdansk (Poland) between 2020 and 2023. Primary outcomes were 30-day mortality and disabling stroke. Secondary outcomes included surgical times, hemodynamics, permanent pacemaker implantation (PPM), length of ICU and hospital stay, new post-operative atrial fibrillation (POAF), post-operative blood transfusion, incidence of acute respiratory distress syndrome (ARDS), rate of continuous renal replacement therapy (CRRT) and/or dialysis, and chest tube output in the first 12-hours after surgery. Results: Nine patients were male, and the mean age was 64.36 years. There were no deaths, while one patient had a disabling stroke postoperatively. Mean cardiopulmonary bypass and cross clamp-times were 136 min and 90 min, respectively. Three patients needed a PPM, 3 patients needed blood transfusions, and 2 developed new onset POAF. Median lengths of ICU and hospital stays were 2 and 12 days, respectively. There was no incidence of paravalvular leak greater than trace and the average transvalvular mean gradient was 12.23 mmHg. Conclusion: The number of patients requiring redo-AVR is increasing. Redo-sternotomy may not be feasible for many patients. This study suggests that the RAMT approach is a safe alternative to redo-sternotomy for patients that require an AVR.

Comparing performance of primary care clinicians in the interpretation of SPIROmetry with or without Artificial Intelligence Decision support software (SPIRO-AID): a protocol for a randomised controlled trial.

INTRODUCTION: Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation). METHODS AND ANALYSIS: A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders. TRIAL REGISTRATION NUMBER: NCT05933694.

Patho-transcriptomic analysis of invasive mucinous adenocarcinoma of the lung (IMA): comparison with lung adenocarcinoma with signet ring cell features (SRCC).

Background: Invasive mucinous adenocarcinoma (IMA) comprises ∼5% of lung adenocarcinoma. There is no effective therapy for IMA when surgical resection is not possible. IMA is sometimes confused with adenocarcinoma with signet ring cell features (SRCC) pathologically since both adenocarcinomas feature tumor cells with abundant intracellular mucin. The molecular mechanisms by which such mucin-producing lung adenocarcinomas develop remain unknown. Methods: Using a Visium spatial transcriptomics approach, we analyzed IMA and compared it with SRCC patho-transcriptomically. Combining spatial transcriptomics data with in vitro studies using RNA-seq and ChIP-seq, we assessed downstream targets of transcription factors HNF4A and SPDEF that are highly expressed in IMA and/or SRCC. Results: Spatial transcriptomics analysis indicated that there are 6 distinct cell clusters in IMA and SRCC. Notably, two clusters (C1 and C3) of mucinous tumor cells exist in both adenocarcinomas albeit at a different ratio. Importantly, a portion of genes (e.g., NKX2-1 , GKN1 , HNF4A and FOXA3 ) are distinctly expressed while some mucous-related genes (e.g., SPDEF and FOXA2 ) are expressed in both adenocarcinomas. We determined that HNF4A induces MUC3A/B and TM4SF4 and that BI 6015, an HNF4A antagonist, suppressed the growth of IMA cells. Using mutant SPDEF that is associated with COVID-19, we also determined that an intact DNA-binding domain of SPDEF is required for SPDEF-mediated induction of mucin genes ( MUC5AC , MUC5B and AGR2 ). Additionally, we found that XMU-MP-1, a SPDEF inhibitor, suppressed the growth of IMA cells. Conclusion: These results revealed that IMA and SRCC contain heterogenous tumor cell types, some of which are targetable.

Voltage-induced modulation of interfacial ionic liquids measured using surface plasmon resonant grating nanostructures.

We have used surface plasmon resonant metal gratings to induce and probe the dielectric response (i.e., electro-optic modulation) of ionic liquids (ILs) at electrode interfaces. Here, the cross-plane electric field at the electrode surface modulates the refractive index of the IL due to the Pockels effect. This is observed as a shift in the resonant angle of the grating (i.e., Δϕ), which can be related to the change in the local index of refraction of the electrolyte (i.e., Δnlocal). The reflection modulation of the IL is compared against a polar (D2O) and a non-polar solvent (benzene) to confirm the electro-optic origin of resonance shift. The electrostatic accumulation of ions from the IL induces local index changes to the gratings over the extent of electrical double layer (EDL) thickness. Finite difference time domain simulations are used to relate the observed shifts in the plasmon resonance and change in reflection to the change in the local index of refraction of the electrolyte and the thickness of the EDL. Simultaneously using the wavelength and intensity shift of the resonance enables us to determine both the effective thickness and Δn of the double layer. We believe that this technique can be used more broadly, allowing the dynamics associated with the potential-induced ordering and rearrangement of ionic species in electrode-solution interfaces.

Improved efficiency using sequential automated immunoassays for syphilis screening in blood donors.

Using sequential immunoassays for the screening of blood donors is well described for viral serology testing but not for the screening of syphilis. In this study, we report the evaluation results and 2-year sequential testing data using two highly sensitive automated serology assays, the Alinity s Syphilis chemiluminescent immunoassay for screening, with all repeatedly reactive samples then tested on the Elecsys Syphilis electrochemiluminescence immunoassay. We screened 1,767,782 blood donor samples between 7 July 2021 and 6 July 2023 and found the Alinity false-positive rate to be low at 0.08% (1,456/1,767,782). The common false-positive rate between the two assays was also low (3.83%, 58/1,514). Concordantly reactive samples were further tested using a Treponema pallidum particle agglutination test, a rapid plasma reagin test, and a fluorescent treponemal antibody absorption test. There were 262/1,376 concordantly reactive Alinity and Elecsys blood donor samples with reactivity on one or more of the confirmatory tests. A total of 26/1,376 donors had a current syphilis infection, 152/1,376 reported a past history of syphilis and had been treated, and 84/1,376 did not report a past history of syphilis. We suggest that future studies could explore the use of sequential immunoassays to aid in the serodiagnosis for syphilis. IMPORTANCE: The serodiagnosis for syphilis usually follows two methodologies-a "traditional" algorithm using a non-treponemal test followed by confirmation using a treponemal test, or a "reverse" algorithm using a treponemal test followed by a non-treponemal test. There are limited reports in the literature of using a modified reverse algorithm (treponemal test followed by a second treponemal test), and to the best of knowledge, there are currently no published articles using two highly sensitive automated immunoassays to aid the serodiagnosis of syphilis. In addition, the Treponema pallidum particle agglutination (TPPA) assay is commonly used as a confirmatory test for the diagnosis of syphilis. With the withdrawal of the TPPA assay from Australia and presumably from the global market also, alternative testing algorithms are now required. This study provides proof of concept for using sequential immunoassays in the diagnosis of syphilis.

A Randomized Controlled Trial of Consent for Patients Undergoing Transobturator Slings.

IMPORTANCE: Improving patients' recall and understanding of their planned surgery is essential for fully informed consent. OBJECTIVE: The objective of this study was to assess if the addition of an information handout to the standard preoperative consent process for the transobturator midurethral sling procedure improved patient understanding, recall, and satisfaction. STUDY DESIGN: This is a randomized controlled trial of adult women undergoing a transobturator midurethral sling procedure for the treatment of stress urinary incontinence. After standard counseling, participants were randomly assigned to either the control or the intervention group, with the latter receiving an extra informational handout detailing surgical information. Before surgery, all participants filled out a questionnaire assessing key points discussed during the surgical consent, which was used to calculate a knowledge score, the primary endpoint. Secondary outcomes included perception of the consent process and patient satisfaction. RESULTS: Of 98 randomized participants (50 control, 48 intervention), knowledge scores were 43% for controls and 57% for the intervention group (P = 0.015). Despite low scores, high self-rated understanding and satisfaction were noted across both groups (78% control, 71% intervention, P = 0.4). Notably, younger individuals, those with some college education, and patients undergoing additional prolapse surgery benefited most from the handout. CONCLUSIONS: The informational handout improved knowledge scores, though overall knowledge scores were low in both groups. High satisfaction and perceived understanding of the planned procedure persisted, but the addition of a handout was not associated with a significant difference in knowledge scores.

Ablation of oligodendrogenesis in adult mice alters brain microstructure and activity independently of behavioral deficits.

Oligodendrocytes continue to differentiate from their precursor cells even in adulthood, a process that can be modulated by neuronal activity and experience. Previous work has indicated that conditional ablation of oligodendrogenesis in adult mice leads to learning and memory deficits in a range of behavioral tasks. The current study replicated and re-evaluated evidence for a role of oligodendrogenesis in motor learning, using a complex running wheel task. Further, we found that ablating oligodendrogenesis alters brain microstructure (ex vivo MRI) and brain activity (in vivo EEG) independent of experience with the task. This suggests a role for adult oligodendrocyte formation in the maintenance of brain function and indicates that task-independent changes due to oligodendrogenesis ablation need to be considered when interpreting learning and memory deficits in this model.

Interpretable artificial intelligence to optimise use of imatinib after resection in patients with localised gastrointestinal stromal tumours: an observational cohort study.

BACKGROUND: Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy. METHODS: In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries. A counterfactual random forest model, which used predictors of recurrence (mitotic count, tumour size, and tumour site) and imatinib duration to infer the probability of recurrence at 7 years for a given patient under each duration of imatinib treatment, was trained in the MSKCC cohort. Optimal policy trees (OPTs), a state-of-the-art interpretable AI-based method, were used to read the counterfactual random forest model by training a decision tree with the counterfactual predictions. The OPT recommendations were externally validated in two cohorts of patients from Poland (the Polish Clinical GIST Registry), who underwent GIST resection between Dec 1, 1981, and Dec 31, 2011, and from Spain (the Spanish Group for Research in Sarcomas), who underwent resection between Oct 1, 1987, and Jan 30, 2011. FINDINGS: Among 1007 patients who underwent GIST surgery in MSKCC, 117 were included in the internal cohort; for the external cohorts, the Polish cohort comprised 363 patients and the Spanish cohort comprised 239 patients. The OPT did not recommend imatinib for patients with GISTs of gastric origin measuring less than 15·9 cm with a mitotic count of less than 11·5 mitoses per 5 mm2 or for those with small GISTs (<5·4 cm) of any site with a count of less than 11·5 mitoses per 5 mm2. In this cohort, the OPT cutoffs had a sensitivity of 92·7% (95% CI 82·4-98·0) and a specificity of 33·9% (22·3-47·0). The application of these cutoffs in the two external cohorts would have spared 38 (29%) of 131 patients in the Spanish cohort and 44 (35%) of 126 patients in the Polish cohort from unnecessary treatment with imatinib. Meanwhile, the risk of undertreating patients in these cohorts was minimal (sensitivity 95·4% [95% CI 89·5-98·5] in the Spanish cohort and 92·4% [88·3-95·4] in the Polish cohort). The OPT tested 33 different durations of imatinib treatment (<5 years) and found that 5 years of treatment conferred the most benefit. INTERPRETATION: If the identified patient subgroups were applied in clinical practice, as many as a third of the current cohort of candidates who do not benefit from adjuvant imatinib would be encouraged to not receive imatinib, subsequently avoiding unnecessary toxicity on patients and financial strain on health-care systems. Our finding that 5 years is the optimal duration of imatinib treatment could be the best source of evidence to inform clinical practice until 2028, when a randomised controlled trial with the same aims is expected to report its findings. FUNDING: National Cancer Institute.

Pectus excavatum: the effect of tricuspid valve compression on cardiac function.

BACKGROUND: Pectus excavatum (PE) is a common congenital chest wall deformity with various associated health concerns, including psychosocial impacts, academic challenges, and potential cardiopulmonary effects. OBJECTIVE: This study aimed to investigate the cardiac consequences of right atrioventricular groove compression in PE using cardiac magnetic resonance imaging. MATERIALS AND METHODS: A retrospective analysis was conducted on 661 patients with PE referred for evaluation. Patients were categorized into three groups based on the degree of right atrioventricular groove compression (no compression (NC), partial compression (PC), and complete compression(CC)). Chest wall indices were measured: pectus index (PI), depression index (DI), correction index (CI), and sternal torsion. RESULTS: The study revealed significant differences in chest wall indices between the groups: PE, NC=4.15 ± 0.94, PC=4.93 ± 1.24, and CC=7.2 ± 4.01 (P<0.0001). Left ventricle ejection fraction (LVEF) showed no significant differences: LVEF, NC=58.72% ± 3.94, PC=58.49% ± 4.02, and CC=57.95% ± 3.92 (P=0.0984). Right ventricular ejection fraction (RVEF) demonstrated significant differences: RVEF, NC=55.2% ± 5.3, PC=53.8% ± 4.4, and CC=53.1% ± 4.8 (P≥0.0001). Notably, the tricuspid valve (TV) measurement on the four-chamber view decreased in patients with greater compression: NC=29.52 ± 4.6; PC=28.26 ± 4.8; and CC=24.74 ± 5.73 (P<0.0001). CONCLUSION: This study provides valuable insights into the cardiac consequences of right atrioventricular groove compression in PE and lends further evidence of mild cardiac changes due to PE.

Potential Cost Savings with 60-day Peripheral Nerve Stimulation Treatment in Chronic Axial Low Back Pain.

INTRODUCTION: Chronic axial low back pain (CLBP) that is not responsive to medication management or physical therapy often requires significant clinical intervention. Several interventional pain management options exist, including a 60-day peripheral nerve stimulation (PNS) treatment. This economic evaluation investigated the potential for projected cost savings associated with prioritizing 60-day PNS treatment relative to a 'standard of care' (SOC) approach (where patients do not have access to 60-day PNS). METHODS: A decision tree (supervised machine learning) model tracked treatment progression across two hypothetical cohorts of US patients with CLBP in whom non-interventional options were ineffective (Cohort A: treatment starting with 60-day PNS followed by any additional interventional and surgical treatments versus Cohort B: standard of care interventional and surgical treatments without access to 60-day PNS). Treatment efficacy estimates were based on published success rates. Conditional on treatment failure, up to two additional interventions were considered within the 12-month time frame in both cohorts. SOC treatment options included epidural injection, radiofrequency ablation (RFA), basivertebral nerve ablation (BVNA), PNS permanent implant (PNS-PI), spinal cord stimulator (SCS) trial/implant, and spinal fusion surgery. Treatment choice probabilities in both cohort algorithms were based on clinician interviews. Costs were based on national Medicare reimbursement levels in the ambulatory surgery center (ASC) setting. Savings reflected the difference in projected costs between cohorts. A Monte Carlo simulation and sensitivity analyses were conducted to generate confidence intervals and identify important inputs. RESULTS: The treatment algorithm which prioritized initial 60-day PNS treatment was projected to save $8056 (95% CI $6112-$9981) per patient during the first year of interventional treatment relative to the SOC approach. CONCLUSIONS: Use of the 60-day PNS treatment as an initial interventional treatment in patients with CLBP may result in significant savings for Medicare. Projected savings may be even larger for commercial payers covering non-Medicare patients.

A hot-Jupiter progenitor on a super-eccentric retrograde orbit.

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.

Comparative analysis of the chimpanzee and human brain superficial structural connectivities.

Diffusion MRI tractography (dMRI) has fundamentally transformed our ability to investigate white matter pathways in the human brain. While long-range connections have extensively been studied, superficial white matter bundles (SWMBs) have remained a relatively underexplored aspect of brain connectivity. This study undertakes a comprehensive examination of SWMB connectivity in both the human and chimpanzee brains, employing a novel combination of empirical and geometric methodologies to classify SWMB morphology in an objective manner. Leveraging two anatomical atlases, the Ginkgo Chauvel chimpanzee atlas and the Ginkgo Chauvel human atlas, comprising respectively 844 and 1375 superficial bundles, this research focuses on sparse representations of the morphology of SWMBs to explore the little-understood superficial connectivity of the chimpanzee brain and facilitate a deeper understanding of the variability in shape of these bundles. While similar, already well-known in human U-shape fibers were observed in both species, other shapes with more complex geometry such as 6 and J shapes were encountered. The localisation of the different bundle morphologies, putatively reflecting the brain gyrification process, was different between humans and chimpanzees using an isomap-based shape analysis approach. Ultimately, the analysis aims to uncover both commonalities and disparities in SWMBs between chimpanzees and humans, shedding light on the evolution and organization of these crucial neural structures.