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Abstract This study investigates the impact of environmental factors on the quality changes of mackerel (Scomber japonicus), a globally significant fish species valued for its high nutritional content, especially its unsaturated fatty acids and proteins. In South Korea, marine products like mackerel undergo auction, sorting, packaging, and transportation. Assessing the fish freshness and quality during these processes, before it reaches consumers, is crucial. This research aimed to track the changes in mackerel quality indicators after the auction and correlate them with the environmental factors affecting transportation. Using a transportation model established for both summer and winter, mackerel samples were categorized by their weight (200 and 300 g). Results show poorer quality indicators in summer compared to winter, particularly in the 200 g group. Microbiological indicators such as the total viable count (0.923) and total coliforms (0.958) were most strongly correlated with the season, whereas the lipid oxidation indicators acid value (0.627) and peroxide value (0.536) were moderately correlated with the season. Interestingly, the wider standard deviation distribution observed in summer suggests that individual mackerel characteristics may influence the degree of quality changes. These findings offer insights into mackerel quality fluctuations during auction and transportation, aiding in future efforts to maintain seafood quality amidst climate change.

Abstract Objective Leucine‐rich glioma‐inactivated 1 (LGI1)‐antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e. Methods Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status. Results A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP‐associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes. Interpretation LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.

Abstract Ultra‐wideband (UWB) systems utilise a broad frequency spectrum to achieve high data transmission rates and enhanced precision, creating a demand for specialised UWB antennas. Circularly Polarised (CP) antennas are considered essential for maintaining robust performance under varied environmental conditions. Among them, the crossed dipole is effective for UWB CP applications, but its relatively large size could limit its use in various systems. A miniaturised crossed dipole design employing the Koch fractal structure is proposed and the measurement results are presented. The prototype antenna achieved an effective bandwidth covering 88% of the frequency range from 1.4 to 3.6 GHz. Additionally, a 4 × 4 array using this design was tested in the same frequency band, demonstrating beam‐steering capabilities up to 30°. The proposed antenna has demonstrated effective deployment in diverse communication systems and phased array applications within ultra‐wideband (UWB) CP environments.

Abstract Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed‐effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two‐compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80‐fold during CPB and warming phases, while the central compartment volume increased 2.74‐fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL‐6, IL‐8, and TNF‐α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target‐controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

Abstract Antiphospholipid syndrome (APS), cryoglobulinemia, and monoclonal gammopathies are variably accompanied by thrombotic complications. We describe a patient with recurrent skin microvascular thrombosis, APS, cryoglobulinemia, marginal zone lymphoma, and IgMκ monoclonal gammopathy, responsive to chemoimmunotherapy. The cryoglobulin fraction contained the IgMκ paraprotein, while antiphospholipid antibodies (aPL) were predominantly in the cryosupernatant. A retrospective analysis of aPL‐positive patients in our institution showed that 8.1% co‐expressed monoclonal gammopathy. These overlap patients had thrombotic complications and most had recurrences. Patients with multiple gammopathies of thrombotic significance may have several autoantibodies and constitute a high‐risk group.

Abstract Background In 2023, the concept of metabolic dysfunction‐associated steatotic liver disease (MASLD) was introduced as an alternative to non‐alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. Methods This cross‐sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of

Abstract Aims This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane oxygenation (VA‐ECMO) weaning success and clinical outcomes in acute myocardial infarction complicated by cardiogenic shock (AMI‐CS) patients. Methods and results A total of 213 patients with AMI‐CS who received VA‐ECMO between January 2010 and August 2021 were enrolled in the institutional ECMO registry. Serial PP and VIS were measured immediately, 12, 24, and 48 h after VA‐ECMO insertion. PP adjusted by VIS was defined as PP/√VIS. The primary outcome was successful VA‐ECMO weaning. Successful weaning from VA‐ECMO was observed in 151 patients (70.9%). Immediately after VA‐ECMO insertion, PP [successful vs. failed weaning, 26.0 (15.5–46.0) vs. 21.0 (12.5–33.0), P = 0.386] and PP/√VIS [11.1 (5.1–25.0) vs. 6.0 (3.1–14.2), P = 0.118] did not differ between the successful and failed weaning groups. Serial PP and PP adjusted by VIS at 12, 24, and 48 h after VA‐ECMO insertion were significantly higher in patients with successful weaning than those with failed weaning [successful vs. failed weaning, 24.0 (4.0–38.0) vs. 12.5 (6.0–25.5), P = 0.007 for 12 h PP, and 10.1 (5.7–22.0) vs. 2.9 (1.7–5.9), P 7). Conclusions PP adjusted by VIS taken 12 h following VA‐ECMO initiation can predict weaning from VA‐ECMO more successfully than PP alone, and its low value was associated with a higher risk of mortality in AMI‐CS patients.

Objective Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. Methods We use Phage Immunoprecipitation‐Sequencing (PhIP‐Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP‐Seq. We next developed a radio‐labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. Results PhIP‐Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free–survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. Conclusion We used PhIP‐Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5‐IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity.

Abstract The PicoCam system is a multi‐camera photogrammetry rig used for generating high‐resolution 3D models of animals in the field, or preserved specimens in laboratory or museum settings. The digital measurement of 3D models is increasingly useful for studying body shape. However, methods that capture sub‐millimetric detail often do so at the cost of portability and versatility; this system aims to bridge this gap. The PicoCam system employs 3D digital photogrammetry, a process that generates accurate, full‐colour, 3D models from sequences of photographs. By using six cameras and a rotating base, the system is able to capture multiple angles in rapid succession—a key advantage for both 3D‐imaging live specimens and efficiently scanning museum specimens. Through the use of macro lenses and high‐resolution camera sensors, this system can capture sub‐millimetric detail without sacrificing portability. In this study, we 3D imaged the bills of 19 species of hummingbirds using the PicoCam system and measured length, height, width, surface area and volume of their bills. We examined eight species in the field and 11 from the Burke Museum in Seattle. We chose Hummingbird bills as a model system, as their fine‐scale interspecific differences in 3D shape can have significant functional and behavioural implications, and could tell us more about how these traits predict habitat and resource use. The prospect of a common 3D‐imaging method for both museum and field use is compelling when documenting structures' shape within and among species. The PicoCam system is also valuable for quantifying the 3D shape of fine‐scale phenotypes (like hummingbird bills) that benefit from digital measurement, preservation, and improved accessibility. Finally, the PicoCam system allows ‘digital 3D collection’, by which the shape of biological structures in the field can be recorded and stored in a public database without the need to collect a specimen. This opens the door to studies in which multiple 3D image captures of the same individual across different time scales permit 3D shape/colour comparisons (e.g. seasonal, ontogenetic changes).

Abstract Spatial modelling approaches to aid land‐use decisions which benefit both wildlife and humans are often limited to the comparison of pre‐determined landscape scenarios, which may not reflect the true optimum landscape for any end‐user. Furthermore, the needs of wildlife are often under‐represented when considered alongside human financial interests in these approaches. We develop a method of addressing these gaps using a case‐study of wild bees in the UK, an important group whose declines may adversely affect both human economies and surrounding ecosystems. By combining the genetic algorithm NSGA‐II with a process‐based pollinator model which simulates bee foraging and population dynamics, Poll4pop, we ‘evolve’ a typical UK agricultural landscape to identify optimum land cover configurations for three different guilds of wild bee. These configurations are compared to those resulting from optimisations for farm income alone, as well as optimisations that seek a compromise between bee populations and farm income objectives. We find that the land cover proportions in landscapes optimised for each bee guild reflect their nesting habitat preferences rather than foraging preferences, highlighting a limiting resource within the study landscape. The spatially explicit nature of these optimised landscapes illustrates how improvement for a given target species may be limited by differences between their movement range and the scale of the units being improved. Land cover composition and configuration differ significantly in landscapes optimised for farm income and bee population growth simultaneously and illustrate how human agents are required to compromise much more when the multifaceted nature of biodiversity is recognised and represented by multiple objectives within an optimisation framework. Our methods provide a way to quantify the extent to which real‐life landscapes promote or compromise objectives for different landscape end‐users. Our investigation suggests that optimisation set‐up (decision‐unit scales, traditional choice of a single biodiversity metric) can bias outcomes towards human‐centric solutions. It also demonstrates the importance of representing the individual requirements of different actors with different landscape‐level needs when using genetic algorithms to support biodiversity‐inclusive decision‐making in multi‐functional landscapes.

Abstract This study investigates predictors of unsatisfactory outcomes in female overactive bladder (OAB) patients treated with oral monotherapy by analyzing skin sympathetic nerve activity (SKNA) using a novel “neuECG” method. The study included 55 newly diagnosed female patients with idiopathic OAB, autonomic function was evaluated using neuECG before treatment initiation, and validated OAB questionnaires and urodynamic studies were administered. Initial monotherapy was administered for the first 4 weeks, with non‐responders defined as patients not achieving satisfactory symptom relief and requiring further treatment. Responders (n = 32) and non‐responders (n = 23) had no significant differences in baseline characteristics or urodynamic parameters; however, non‐responders exhibited significantly higher baseline average SKNA (aSKNA) (1.36 ± 0.49 vs. 0.97 ± 0.29 μV, p = 0.001), higher recovery aSKNA (1.28 ± 0.46 vs. 0.97 ± 0.35 μV, p = 0.007), and a lower stress/baseline ratio of aSKNA (1.05 ± 0.42 vs. 1.26 ± 0.26, p = 0.029). Baseline aSKNA had the highest predictive value for monotherapy refractoriness in OAB (AUROC = 0.759, p = 0.001), with an optimal cut‐off point of >1.032 μV. These findings suggest that elevated pre‐treatment aSKNA can predict resistance to oral monotherapy in OAB, warranting close monitoring and proactive treatment strategies for patients with high aSKNA.

Abstract Diagnosing post‐gastrectomy hypoglycemia is challenging, often relying on medical history with documented low plasma glucose levels. Here, we present three cases of patients who presented a high probability of post‐gastrectomy hypoglycemia diagnosed and managed successfully using “theragnostic” continuous glucose monitoring and alpha‐glucosidase inhibitors. In the first week, patients maintained their current lifestyle without medical intervention; in the second week, voglibose 0.2 mg before meals was prescribed. Continuous glucose monitoring data from the first week confirmed the diagnosis with multiple hypoglycemic events after postprandial peaks, whereas data from the second week showed reduced hypoglycemic events and lower glycemic variability, demonstrating voglibose's therapeutic effect. This report highlights the effective management of post‐gastrectomy hypoglycemia using voglibose and theragnostic continuous glucose monitoring, showing its potential benefits and safety for similar cases.

Abstract Intelligent fault diagnosis for wind energy systems requires identifying unique characteristics to differentiate various fault types effectively, even when data discrepancy occurs due to the unpredictable and dynamic nature of its environment. This article addresses some of the challenges of fault classification in wind energy systems by proposing an integrated approach that combines deep learning features with a resampled supervisory control and data acquisition (SCADA) dataset. The methodology involves resampling the imbalanced SCADA dataset using synthetic minority oversampling technique (SMOTE) and near‐miss undersampling techniques, extracting deep learning features using deep convolutional neural network, and feeding them into an XGBoost (extreme gradient boosting) classifier with tuned parameters using adaptive elite‐particle swarm optimization (AEPSO). The effectiveness of the proposed method is demonstrated through validation conducted on a different imbalanced dataset showing superior performance metrics in terms of accuracy. Additionally, the study contributes to methodological advancements in wind turbine fault diagnosis by providing a rigorous framework for fault classification. It is confirmed that utilizing the extracted deep learning features into the resampled data can significantly affect the classification performance metrics. Furthermore, the proposed integrated approach shows significance for fault diagnosis enhancement in wind energy systems and advancing the field towards more efficient and reliable operation.

Abstract Objectives Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico‐striatal‐thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP. Methods Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS). Results White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways. Interpretation The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well‐described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes.

Abstract Background Paranasal sinus retention cysts are non‐neoplastic psuedocysts that accumulate nasal fluids. Since most of these cysts are incidentally diagnosed and may even diminish spontaneously, no further diagnosis or therapies are needed for most patients. In contrast, when an abrupt, unilateral, watery nasal discharge is noticed, cerebrospinal fluid (CSF) rhinorrhea should be suspected, which is a true “red flag sign,” since ignored CSF rhinorrhea may be fatal. Case Report Herein we report a case of a 42‐year‐old male with an acute, unilateral, profusely projectile serous rhinorrhea without any trauma or sinonasal surgery history. Following an urgent computed tomography, no skull base abnormalities were seen, ruling out the possibility of CSF rhinorrhea. However, a “ruptured” retention cyst in the maxillary sinus was noticed. Thus, it was concluded that the patient’s projectile unilateral serous rhinorrhea was due to a rupturing of the retention cyst in the affected maxillary sinus. The patient remained asymptomatic afterwards, negating the surgical removal or further follow‐up visits. Conclusion While the majority of paranasal sinus retention cyst cases are symptomless, spontaneous rupture of these cysts may take place and result in a sudden and vigorous release of nasal secretions, mimicking CSF rhinorrhea, as seen in our case.

Abstract High‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

Abstract Introduction Relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B‐ and T‐ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L‐VCR and VEN for patients with r/r B‐or T‐cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644). Methods In a 3+3 dose escalation design, r/r ALL subjects were given single‐agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L‐VCR at 2.25 mg/m2 IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination. Results Among the 18 patients in phase I, grade ≥ 3 treatment‐related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose‐limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty‐two percent of evaluable patients (N = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD). Conclusion The combination of VEN and L‐VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L‐VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.

Abstract Objectives The objective of this study is to report the pilot phase of the Targeted Prostate Health Check programme that aims to identify men in the Surrey and Sussex region who have prostate cancer and who failed to be detected during the Covid era. Subjects and methods Men aged 50 to 70, or 45 to 70 if Black or with a family history of prostate cancer, were identified from participating general practitioner (GP) records. Short message service (SMS) texts invited men to visit www.talkprostate.co.uk for information on prostate cancer and give consent to prostate‐specific antigen (PSA) checks coordinated by a third‐party virtual healthcare provider. Elevated age‐related PSA levels, or levels below age‐related thresholds but at 3 ng/mL or more, triggered referral to a rapid access urology clinic. GPs were informed of the results. Results From 1842 text messages inviting 1549 people, 544 men consented to a PSA check. From 500 phlebotomy appointments, 485 (30% of invited men) took the PSA test of whom 68 (14%) were referred with an elevated PSA. After clinical review with multiparametric magnetic resonance imaging (mp‐MRI), 22 patients underwent transperineal biopsies, and prostate cancer was detected in 18 men of whom 17 (95%) had clinically significant cancer. Conclusion Our Targeted Prostate Cancer Health Check system identifies men at risk without burdening primary care. Awareness on prostate cancer risk was raised in 1549 invited men, half of whom were further educated via the registration website. One third of invited men were checked in whom clinically significant prostate cancer was found in 3.5%.

MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC's function from being a gene‐specific transcription factor to an essential stress resilience factor. In highly proliferating cells, MYC preserves cell integrity by promoting DNA repair at core promoters, protecting stalled replication forks, and/or preventing transcription‐replication conflicts. Furthermore, an increasing body of evidence demonstrates that MYC not only promotes tumorigenesis by driving cell‐autonomous growth, but also enables tumors to evade the host's immune system. In this review, we summarize our current understanding of how MYC impairs antitumor immunity and why this function is evolutionarily hard‐wired to the biology of the MYC protein family. We show why the cell‐autonomous and immune evasive functions of MYC are mutually dependent and discuss ways to target MYC proteins in cancer therapy.

Abstract Objective Vagus nerve stimulation (VNS) Therapy is routinely indicated for people with drug‐resistant epilepsy (DRE). We analyzed the baseline characteristics of individuals receiving the recently released VNS models and identified factors associated with early or late implantation. Methods The Comprehensive Outcomes Registry of subjects with Epilepsy (CORE‐VNS), a prospective observational study evaluating the clinical and psychosocial outcomes of VNS Therapy®, is following participants for up to 60 months after VNS implantation. In this analysis, we used Cox proportional hazards model to identify baseline characteristics associated with the time from diagnosis to first implantation. Results Of the 819 enrolled, 792 (96.7%) participants implanted with a VNS device were evaluated. 529 (64.6%) underwent the first implantation and 263 (32.1%) a re‐implantation. Participants' median age at first implant was 24 years; 492 (62.1%) were ≥18 years old and 166 (20.3%) were

Pectocin M1 (PM1), the bacteriocin from phytopathogenic Pectobacterium carotovorum which causes soft rot disease, has a unique ferredoxin domain that allows it to use FusA of the plant ferredoxin uptake system. To probe the structure‐based mechanism of PM1 uptake, we determined the X‐ray structure of full‐length PM1, containing an N‐terminal ferredoxin and C‐terminal catalytic domain connected by helical linker, at 2.04 Å resolution. Based on published FusA structure and NMR data for PM1 ferredoxin domain titrated with FusA, we modeled docking of the ferredoxin domain with FusA. Combining the docking models with the X‐ray structures of PM1 and FusA enables us to propose the mechanism by which PM1 undergoes dynamic domain rearrangement to translocate across the target cell outer membrane.

Abstract Background Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co‐chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo. Methods We generated mouse strain with Dnaja3 heterozygosity (HSA‐Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA‐Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA‐Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short‐term and long‐term GMI treatment were administrated intraperitoneally to the HSA‐Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively. Results Muscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P

Abstract Aims Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Abstract Aims Sex differences in long‐term post‐discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world‐wide implementation of guideline‐directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. Methods and results Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P 50%) than men (P 50%) and HF with mildly reduced EF (40%–50%), but not in HF with reduced EF (

Abstract Aims Catheter ablation (CA) of atrial fibrillation (AF) improves left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF). The impact of ST‐segment depression before CA on LVEF recovery and clinical outcomes remains unknown. In the present study, we aimed to investigate the relationship between ST‐segment depression during AF rhythm before CA and improvement in the LVEF and clinical outcomes in persistent atrial fibrillation (PerAF) patients with HFrEF. Methods and results The present study included 122 PerAF patients (male; 98 patients, 80%, mean age: 69 [56, 76] years) from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry who had LVEF

Abstract Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) is diagnosed by serum MOG‐immunoglobulin G (MOG‐IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG‐IgG. Only 7/1016 (0.7%) seronegative patients had CSF‐restricted MOG‐IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF‐restricted MOG‐IgG had a low sensitivity (2.63%, 95%CI 0.55–7.50%) and low positive predictive value (1.97%, 95%CI 0.45–8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF‐restricted MOG‐IgG in patients without clinico‐radiological features consistent with MOGAD.

Abstract Objective The objective was to determine the mean duration of diagnosis delay for patients with myasthenia gravis from five European countries and explore the impact of >1 year diagnosis delay. Methods Patients with myasthenia gravis (N = 387) from Europe (France/Germany/Italy/Spain/United Kingdom) and their physicians participated in the Adelphi Real World Myasthenia Gravis Disease Specific Programme™. Diagnosis delay (time from symptom onset to diagnosis) was calculated and characteristics described for patients experiencing >1 year and ≤1 year diagnosis delay. Denominators varied according to outcome as missing data were not imputed. Results Mean (standard deviation) diagnosis delay was 363.1 (520.9) days, and 27.1% (105 out of 387) of patients experienced diagnosis delay >1 year. Among patients with >1 year and ≤1 year diagnosis delay, respectively, 69.2% (72 out of 104) and 17.4% [45 out of 259] had initially received a different diagnosis (physician‐reported); 40.0% (42 out of 105) and 24.1% (68 out of 282) were Myasthenia Gravis Foundation of America class III at the time of the survey (physician‐reported); 72.4% (76 out of 105) and 61.3% (173 out of 282) had fatigue (subjective physician reporting from a pre‐selected list of symptoms); 30.5% (32 out of 105) and 17.4% (49 out of 282) had anxiety and 21.9% (23 out of 105) and 13.1% (37 out of 282) had depression (both subjective physician reporting from a pre‐selected list, Likert‐style); and mean (standard deviation) MG‐QoL‐15r score was 14.4 (5.50) and 12.6 (7.84) (self‐reported by N = 43 and N = 74 patients, respectively). Interpretation More than a quarter of patients with myasthenia gravis experienced diagnosis delay of >1 year. These patients had a different clinical profile with regards to severity, symptoms, comorbidities and MG‐QoL‐15r score, compared with patients experiencing ≤1 year diagnosis delay.

Abstract The basal Taebaek Group (Myeonsan and Myobong formations) illustrates second‐order transgression on the eastern Sino‐Korean Block during the early–middle Cambrian (Stage 3?–Wuliuan). The irregular palaeotopography of Precambrian basement led to the development of localised alluvial fans and fan deltas. As transgression continued, tidally influenced estuarine and associated shallow subtidal flats developed. Continued transgression resulted in a relatively deep subtidal environment, with postulated carbonate shoals serving as barriers. Stacking of facies indicates a general deepening‐upward trend, transitioning from terrestrial–nearshore to marine environments dominated by tidal effects. The study area subsequently experienced shallowing, leading to the emergence of tidal inlet and dune environments. Siliciclastic input was attenuated, facilitating the development of carbonate shoal complexes. The overall transgressive succession of the basal Taebaek Group aligns with similar sequences observed in the Sino‐Korean Block and western Laurentia, where the lowermost Cambrian strata which formed in various depositional environments on the uneven basement rocks were followed by extensive tide‐dominated siliciclastic successions. These successions were then overlain by epeiric carbonate platforms that developed synchronously across the area as siliciclastic input diminished with the continued transgression. This comparison demonstrates that the transgressive sequences in the Sino‐Korean Block and western Laurentia can be understood within a framework that explains how extensive Cambrian carbonate platforms initially developed due to a second‐order eustatic sea‐level rise during the Cambrian greenhouse period.

Objective In the face of the ongoing circulation of SARS‐CoV‐2, the durability of neutralization post–COVID‐19 vaccination in immune‐mediated inflammatory disease (IMID) is a key issue, as are the effects of medications. Methods Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log‐transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild‐type and Omicron strains BA.1 and BA.5. Results Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild‐type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron‐specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID‐19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti–tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses. Conclusion Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron‐specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID‐19 immunity.

Abstract Introduction There are overlapping features between inflammatory myopathies and muscular dystrophies, particularly laminopathies. Key features that characterize laminopathies include axial and proximal weakness, contractures, and cardiac abnormalities. Methods/Results A 12‐year‐old girl diagnosed with juvenile dermatomyositis as a child presented with cardiac failure and was found to have an LMNA likely pathogenic variant, with a phenotype most consistent with Emery–Dreifuss muscular dystrophy type 2. Discussion The spectrum of clinical features of LMNA‐related muscular dystrophies can mimic or present with inflammatory myopathy‐like features. Early identification of LMNA‐related muscular dystrophies is crucial to ensure appropriate cardiac screening and prevent devastating cardiac complications.

Abstract A 14‐year‐old spayed female Miniature Pinscher presented with tongue curling, dysphagia, hypersalivation, and sublingual gland swelling. Comprehensive evaluation, including neurologic and musculoskeletal examinations, blood work, and urinalysis, revealed no abnormalities other than tongue‐related signs. Magnetic resonance imaging (MRI) revealed a multilobed cystic structure in the occipito‐atlanto‐axial joint, compressing the right hypoglossal canal. The lesion appeared cerebrospinal fluid (CSF)‐like on T1‐weighted and T2‐weighted images, and hyperintense compared with CSF on fluid‐attenuated inversion recovery T2‐weighted images. The scans suggested mucinous content with enhanced peripheral areas on contrast‐enhanced images. Surgical removal and drainage of this cyst were performed, and clinical signs improved markedly. The dorsal cyst was tentatively diagnosed as a ganglion cyst based on histopathologic and imaging findings. Ganglion cysts should be considered in the differential diagnosis for dogs with similar MRI findings and neurologic signs.

Abstract Background Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal‐related flux of GB bile decreases serum FGF19 concentrations. Objective Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. Animals Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty‐two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. Methods Prospective cross‐sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. Results Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8‐67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5‐285.1). Conclusions and Clinical Importance In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Abstract The gut microbiota undergoes substantial development from birth, and its development in the initial years of life has a potentially lifelong effect on the health of the individual. However, various factors can disrupt the development of the gut microbiota, leading to a condition known as dysbiosis, particularly in preterm infants. Current studies involving adults have suggested that the gut microbiota not only influences the gut but also has multidimensional effects on remote organs; these pathways are often referred to as the gut–organ axis. Imbalance of the gut microbiota may lead to the development of multiple diseases. Recent studies have revealed that gut dysbiosis in preterm infants may cause several acute morbidities—such as necrotizing enterocolitis, late‐onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity—and it may also influence long‐term outcomes including neurodevelopment and somatic growth. This review mainly presents the existing evidence regarding the relationships between the gut microbiota and these morbidities in preterm infants and explores the role of the gut–organ axis in these morbidities. This paper thus offers insights into the future perspectives on microbiota interventions for promoting the health of preterm infants.

Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life‐long insulin replacement. Exogenous multiple‐daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real‐time changing life‐log variables, such as activity, diet and stress, which results in recurrent hypo‐ and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose‐stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one‐to‐one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia.

ABSTRACT Introduction Glucagon‐like peptide 1 receptor agonists (GLP1Ras) have emerged as pivotal agents in diabetes management and organ protection. However, their use is limited due to the necessity for injectable administration. The advent of the first oral GLP1Ra (oral semaglutide) in Japan since 2021 is expected to expand its usage. The aim of this study is to survey the efficacy and tolerability of oral semaglutide in clinical practice. Materials and Methods We retrospectively analyzed 120 outpatients diagnosed with type 2 diabetes mellitus who had received oral semaglutide for >6 months. Changes in clinical parameters during oral semaglutide treatment from baseline to 12 months were analyzed. The inverse probability weighting method using the propensity score was used to evaluate the differences in clinical parameters at 6 months after treatment, based on the patients’ obesity levels. Results Body weight (BW), glycated hemoglobin A1c (HbA1c), and alanine aminotransferase (ALT) levels at baseline decreased significantly after treatment compared with those at 12 months (P

Abstract Introduction IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear. Methods In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2R172K transgenic mice. Results We found that thrombopoietin (TPO)‐overexpressed Idh2R172K (Idh2R172K + TPO) mice had accelerated progression to MF, compared with TPO‐overexpressed Idh2‐wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single‐cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2R172K + TPO group. Furthermore, Idh2R172K mice at age of 18 months had larger spleens, increased S100a8/a9‐Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations. Conclusion Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2R172K + TPO mice.

Abstract Background There is limited research on the intra‐individual efficacy of ventricular pacing minimization algorithms developed by Biotronik—the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual‐chamber pacemaker. Methods The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3‐month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow‐up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Abstract Objective Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients. Methods We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti‐seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains. Results A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12‐q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood‐onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies. Significance Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early‐onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background. Plain Language Summary This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood‐onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.

Abstract Background Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin‐2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored. Methods We retrospectively analyzed 191 patients with SCLC (72 with limited‐stage [LD] and 119 with extensive‐stage) treated using platinum‐based chemotherapy. Lipocalin‐2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin‐2 and neutrophil‐to‐lymphocyte ratio (NLR) were determined using time‐dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia. Results In LD‐SCLC, high lipocalin‐2 expression was associated with worse progression‐free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin‐2 expression. Patients were stratified into three prognostic groups by combining lipocalin‐2 with NLR: low lipocalin‐2/low NLR, high lipocalin‐2/low NLR or low lipocalin‐2/high NLR, and high lipocalin‐2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin‐2 with the pectoralis muscle index. High lipocalin‐2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin‐2 in extensive‐stage SCLC. Conclusions High lipocalin‐2 expression is potentially associated with poorer survival in LD‐SCLC. Combining lipocalin‐2 with other inflammation‐related markers could improve prognostic stratification.

Abstract Background Hypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post‐AFCA reverse remodeling and AF recurrence based on HCM presence and subtype. Methods Among 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age‐, gender‐, and AF type‐matched. Between AF‐HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1‐year follow‐up, and procedural outcomes over the course of follow‐up between two groups. Results A total of 122 AF‐HCM patients and 318 control patients were included. AF‐HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p

Abstract Aims/Introduction To investigate the long‐term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. Materials and Methods Donor porcine islets were obtained from wild‐type, α1,3‐galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate‐chitosan (AC), alginate‐perfluorodecalin (A‐PFD) and AC‐perfluorodecalin (AC‐PFD) encapsulated porcine islets were transplanted into diabetic mice. Results In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC‐PFD capsules showed the most favorable long‐term outcomes, maintaining normal blood glucose levels for 180 days. A‐PFD capsules showed comparable results to AC‐PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild‐type porcine islets. Conclusion The AC‐PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long‐term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.

Abstract Interface engineering is pivotal for enhancing the performance and stability of devices with layered structures, including solar cells, electronic devices, and electrochemical systems. Incorporating the interfacial dipole between the bulk layers effectively modulates the energy level difference at the interface and does not significantly influence adjacent layers overall. However, interfaces can drastically affect adjoining layers in ultrathin devices, which are essential for next‐generation electronics with high integrity, excellent performance, and low power consumption. In particular, the interfacial effect is pronounced in ultrathin semiconductors, which have a weak electric field screening effect. Herein, the substantial interfacial impact on the ultrathin silicon is shown, the p‐ to n‐type inversion of the semiconductor solely through the deposition of a self‐assembled monolayer (SAM) without external bias. The effects of SAMs with different interfacial dipoles are investigated by using Hall measurement and surface analytic techniques, such as UPS, XPS, and KPFM. Furthermore, the lateral electronic junction of the ultrathin silicon is engineered by the regioselective deposition of SAMs with opposite dipoles, and the device exhibits rectification behavior. When the interfacial dipole of SAM is manipulated, the rectification ratio changes sensitively, and thus the fabricated diode shows potential to be developed as a sensing platform.

ABSTRACT Introduction People with dementia of all ages have a human right to equal access to quality health care. Despite evidence regarding its effectiveness, many people living with dementia are unable to access rehabilitation for promoting function and quality of life. Conducted in Australia, this study was designed to (1) explore barriers to access to dementia rehabilitation and (2) identify solutions that improve access to rehabilitation. Methods People living with dementia (n = 5) and care partners (n = 8) and health professionals (n = 13) were recruited nationally. Experience‐based codesign across three virtual workshops was used to understand barriers and design solutions to improve access to rehabilitation treatments. Socio‐ecological analyses, using the Levesque Access to Health care framework, were applied to findings regarding barriers and to aid selection of solutions. Results There was high attendance (92.3%) across the three workshops. Barriers were identified at a user level (including lack of knowledge, transport, cost and difficulty navigating the health, aged care and disability sectors) and health service level (including health professional low dementia knowledge and negative attitudes, inequitable funding models and non‐existent or fragmented services). Solutions focused on widespread dementia education and training, including ensuring that people with dementia and their care partners know about rehabilitation therapies and that health professionals, aged care and disability co‐ordinators know how to refer to and deliver rehabilitation interventions. Dementia care navigators, changes to Australia's public funding models and specific dementia rehabilitation programmes were also recommended. Conclusions Barriers to accessing rehabilitation for people with dementia exist at multiple levels and will require a whole‐community and systems approach to ensure change. Patient or Public Contribution People with living experience (preferred term by those involved) were involved at two levels within this research. A Chief Investigator living with dementia was involved in the design of the study and writing of the manuscript. People with living experience, care partners and service providers were participants in the codesign process to identify barriers and design potential solutions.

Abstract Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon‐gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell‐extrinsic, tumour‐suppressive role within EVs. Moreover, the delivery of MEK1 to tumour‐associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti‐tumour immunity.

Abstract Aim To evaluate nurses' workload during the coronavirus disease 2019 (COVID‐19) pandemic and to identify their perception of medical serviced robots (MSRs) that may help with or replace the tasks of nurses in negative‐pressure isolated wards and general wards. Design Cross‐sectional survey. Methods A researcher‐made questionnaire was applied that assessed nurses' current workload and their attitudes towards and perceptions of MSRs. A visual analogue scale (VAS) from 1 to 10 was used to assess workload. Perceptions evaluated on a 5‐point Likert scale ranging from one point for ‘strongly disagree’ to five points for ‘strongly agree’. A higher VAS score indicated a higher workload. On the other hands, a higher Likert score indicated a more positive perception and three points was neutral. The questionnaire was conducted on 150 nurses in negative‐pressure isolated wards for the management of COVID‐19 and 150 nurses in general wards. Quota sampling technique was used as sampling technique. Data analysis was performed through independent t‐tests, chi‐square tests and two‐tailed tests. The p‐value

Abstract In this study, a multiple‐resonance (MR) core structure is developed with a spin‐flip‐restricted emission mechanism based on a fused indolo[3,2,1‐jk]carbazole (ICz) framework as emitters to improve the lifetime of blue organic light‐emitting diodes. The molecular skeleton modulation approach applied to the conjugated π‐system effectively stabilizes the triplet energy of the fused ICz emitters and narrows the full‐width‐at‐half maximum (

Abstract Carbon nanotubes (CNTs), owing to their superior electrical and mechanical properties, are a promising alternative to nonmetallic electrically conducting materials. In practice, cellulose as a low‐cost sustainable matrix has been used to prepare the aqueous dispersion of cellulose‐CNT (C‐CNT) nanocomposites. However, the compatibility with conventional solution‐processing and structural rearrangement for improving conductivity has yet to be determined. Herein, a straightforward route to prepare a conductive composite material from single‐walled CNTs (SWCNTs) and natural pulp is reported. High‐power shaking realizes the self‐alignment of individual SWCNTs in a cellulose matrix, resulting from the structural change in molecular orientations owing to countless collisions of zirconia beads in the aqueous mixture. The structural analysis of the dried C‐CNT films confirms that the entanglement and dispersion of C‐CNT nanowires determine the mechanical and electrical properties. Moreover, the rheological behavior of C‐CNT inks explains their coating and printing characteristics. By controlling shaking time, the electrical conductivity of the C‐CNT films with only 9 wt.% of SWCNTs from 0.9 to 102.4 S cm−1 are adjusted. the optimized C‐CNT ink is highly compatible with the conventional coating and printing processes on diverse substrates, thus finding potential applications in eco‐friendly, highly flexible, and stretchable electrodes is also demonstrated.