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Background: Individuals with Alzheimer's disease and related dementias (ADRD) often face high acute care clinical utilization and costs with unclear benefits in survival or quality of life. The emergency department (ED) is frequently the site of pivotal decisions in these acute care episodes. This study uses national Medicare data to explore this population's ED utilization. Methods: Retrospective cohort study of persons aged ≥66 years enrolled in traditional Medicare with a Chronic Condition Warehouse diagnosis of dementia. Primary 1‐year outcome measures included ED visits with and without hospitalization, ED visits per 100 days alive, and health‐care costs. A multivariate random effects regression model (clustered by county of residence), adjusted for sociodemographics and comorbidities, examined how place of care on January 1, 2018, was associated with subsequent ED utilization. Results: In 2018, 2,680,006 ADRD traditional Medicare patients (mean age 82.9, 64.2% female, 9.4% Black, 6.2% Hispanic) experienced a total of 3,234,767 ED visits. Over half (52.2%) of the cohort experienced one ED visit, 15.5% experienced three or more, and 37.1% of ED visits resulted in hospitalization. Compared with ADRD patients residing at home without services, the marginal difference in ED visits per 100 days alive varied by location of care. Highest differences were observed for those with hospitalizations (0.48 visits per 100 days alive, 95% confidence interval [CI] 0.47–0.49), skilled nursing facility (rehab/skilled nursing facility [SNF]) stays (0.27, 95% CI 0.27–0.28), home health stays (0.25, 95% CI 0.25–0.26), or observation stays (0.82, 95% CI 0.77–0.87). Similar patterns were observed with ED use without hospitalization and health‐care costs. Conclusions: Persons with ADRD frequently use the ED—particularly those with recent hospitalizations, rehab/SNF stays, or home health use—and may benefit from targeted interventions during or before the ED encounters to reduce avoidable utilization and ensure goal‐concordant care. [ABSTRACT FROM AUTHOR]

Alternating‐rich copolymer of vinylboronic acid pinacol ester (VBpin) and maleic anhydride (MAH) was found to catalyze direct dehydrative esterification of carboxylic acid and alcohol. The key to the catalytic function is the activation of the MAH unit by the neighboring Lewis acidic boron directly connected to the backbone through the formation of five‐membered ring. The effects of the side‐chain cooperation were clarified through comparisons with the polymers having similar structures and a conventional titanium catalyst as well as the analyses of reactions with carboxylic acid or alcohol. The catalytic activity was enhanced as the molecular weight was higher, which is owing to the structural feature that boron is directly attached to the backbone. The cooperative catalysis is of interest because of its conceptual similarity with enzyme. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of pre‐ and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot‐assisted laparoscopic radical prostatectomy (RARP). Patients and Methods: We carried out a single‐blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24‐h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. Results: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0–908.0] g vs 21.0 [0.0–750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24‐h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. Conclusion: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra‐anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP. [ABSTRACT FROM AUTHOR]

The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) is the primary effort of CMIP6 (Coupled Model Intercomparison Project–Phase 6) focusing on ice sheets, designed to provide an ensemble of process‐based projections of the ice‐sheet contribution to sea‐level rise over the twenty‐first century. However, the behavior of the Antarctic Ice Sheet beyond 2100 remains largely unknown: several instability mechanisms can develop on longer time scales, potentially destabilizing large parts of Antarctica. Projections of Antarctic Ice Sheet evolution until 2300 are presented here, using an ensemble of 16 ice‐flow models and forcing from global climate models. Under high‐emission scenarios, the Antarctic sea‐level contribution is limited to less than 30 cm sea‐level equivalent (SLE) by 2100, but increases rapidly thereafter to reach up to 4.4 m SLE by 2300. Simulations including ice‐shelf collapse lead to an additional 1.1 m SLE on average by 2300, and can reach 6.9 m SLE. Widespread retreat is observed on that timescale in most West Antarctic basins, leading to a collapse of large sectors of West Antarctica by 2300 in 30%–40% of the ensemble. While the onset date of retreat varies among ice models, the rate of upstream propagation is highly consistent once retreat begins. Calculations of sea‐level contribution including water density corrections lead to an additional ∼10% sea level and up to 50% for contributions accounting for bedrock uplift in response to ice loading. Overall, these results highlight large sea‐level contributions from Antarctica and suggest that the choice of ice sheet model remains the leading source of uncertainty in multi‐century projections. Plain Language Summary: Numerical models simulating the evolution of the Antarctic Ice Sheet have mostly focused on the twenty‐first century. How the ice sheet will evolve after 2100 remains highly uncertain, as several instability mechanisms could develop and destabilize vast regions of Antarctica. We investigate here the behavior of the Antarctic Ice Sheet until 2300 using an ensemble of 16 different ice flow models. The results show that the Antarctic contribution to sea‐level rise remains limited until 2100 but increases rapidly afterward. The ice retreats in most basins of the West Antarctic Ice Sheet, and some numerical experiments suggest a near‐complete collapse of this region by 2300. The time when these glaciers start retreating varies depending on the choice of ice flow model, but the speed at which they retreat is consistent among the models once the retreat begins. On a multi‐century timescale, the choice of ice sheet model remains a leading source of uncertainties. Key Points: Antarctic Ice Sheet mass loss and associated uncertainty increase sharply after 2100Ice streams feeding the Ross and Ronne ice shelves experience considerable and consistent grounding line retreat for all ice sheet modelsOn multi‐centennial timescales, uncertainty in mass loss remains dominated by the choice of ice flow model, followed by the climate forcing [ABSTRACT FROM AUTHOR]

Background: Research to date has detailed numerous challenges in emergency department (ED) communication with persons living with dementia (PLWD) and their caregivers. However, little is known about communication experiences of individuals belonging to minoritized racial and ethnic groups, who are disproportionately impacted by dementia and less likely to be included in dementia research. Methods: We conducted semi‐structured interviews with 29 caregivers of PLWD from two urban academic hospital EDs with distinct patient populations. The first site is an ED in the Northeast serving a majority White, English‐speaking, and insured population. The second site is an ED in the South serving a majority Black and/or Hispanic, Spanish‐speaking, and underinsured population. Interviews lasted an average of 25 min and were digitally recorded and transcribed. We used an inductive approach to analyze interview transcripts for dominant themes and compared themes between sites. Results: Our sample included caregivers of diverse racial and ethnic backgrounds. Caregivers cared for PLWD who spoke English, Spanish, Arabic, Chinese, and Vietnamese. We identified three themes. First, caregiver advocacy was central to experiences of ED communication, particularly when PLWD primarily spoke a non‐English language. Second, routine care plans did not address what mattered most to participants and PLWD. Participants felt that care arose from protocols and did not address what mattered most to them. Third, White English‐speaking caregivers in Site 1 more commonly expected ED staff to engage them in care decision‐making than Black, Hispanic, Asian, and Middle Eastern caregivers in Site 2. Conclusion: Language barriers amplify the higher intensity care needed by PLWD in the ED. Strategies should be developed for communicating with PLWD and caregivers about what matters most in their ED care. [ABSTRACT FROM AUTHOR]

We studied electrochemical behavior of UVO2+/UVIO22+ in non‐aqueous liquid electrolytes to clarify what is required to attain its reversibility for utilizing depleted U in a redox‐flow battery. To transfer knowledge from former pyrochemical systems in high temperature molten salts, 1‐ethyl‐3‐methylimidazolium bis(trifluoromethyl)sulfonylamide ([emim]Tf2N) ionic liquid was employed here. As a result, a reversible redox reaction of the UVO2+/UVIO22+ was successfully observed on a glassy carbon working electrode under presence of Cl− in [emim]Tf2N, where [UVIO2Cl4]2−+e−=[UVO2Cl4]3− occurs after stabilization of both U oxidation states by the Cl− coordination. The observed electrochemical responses are rather sensitive to an electrode material, so that cyclic voltammograms on a Pt working electrode were actually irreversible. To improve diffusivity of solutes, viscosity (η) of [emim]Tf2N diluted with an auxiliary molecular solvent, N,N‐dimethylformamide (DMF), was examined under absence and presence of Cl−. When the mole fraction of DMF (xDMF) is 0.769, η of the mixture becomes sufficiently low to be utilized as a liquid electrolyte. Finally, we have succeeded in demonstrating a reversible redox reaction of [UVIO2Cl4]2−+e−=[UVO2Cl4]3− in the [emim]Tf2N‐DMF (50 : 50 v/v, xDMF=0.769) liquid electrolyte containing [Cl−]=0.519 M, where η=6.2 mPa ⋅ s. [ABSTRACT FROM AUTHOR]

Halogenation of non‐fused ring electron acceptors (NFREAs) plays an important role in regulating their optoelectronic properties. However, the underlying mechanisms and their impact on the performance of organic solar cells (OSCs) have remained unclear. Herein, a series of halogenated NFREAs incorporating F, Cl, and Br, are prepared to study their effect on crystallization kinetics, phase separation, molecular packing, and charge transport. Among various halogenation strategies, chlorination minimizes the Coulomb attractive energy between donor and acceptor, thereby facilitating exciton dissociation. In situ UV–vis absorption tests reveal that chlorinated acceptors exhibit a longer crystallization time, effectively suppressing excessive molecular aggregation and enhancing overall crystallinity. Additionally, chlorinated acceptors exhibit a longer exciton diffusion length, which promotes exciton dissociation while mitigating charge recombination in the devices. Consequently, two chlorinated NFREAs, TCN‐Cl, and PCN‐Cl, yield an impressive power conversion efficiency (PCE) of 14.85% and 15.30%, respectively, when blended with PM6 and J52 donors. These values represent the highest reported PCEs to date for NFREAs with A‐π‐A'‐π‐A and A‐π‐D‐π‐A structures. The study elucidates the crucial role of chlorination in extending exciton diffusion length and crystallization time. These effects significantly benefit phase separation within the active layers, enhance charge separation, and suppress recombination for achieving high‐efficiency OSCs. [ABSTRACT FROM AUTHOR]

Background: Vertical run‐length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end‐stage renal disease (ESRD) remains unclear. Purpose: To evaluate the prognostic value of VRLN MRI in patients with ESRD. Study Type: Prospective. Population: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). Field Strength/Sequence: 3.0 T/steady‐state free precession sequence, modified Look‐Locker imaging. Assessment: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid‐ventricular short‐axis slice of T1 mapping. Left ventricular (LV) mass, LV end‐diastolic and end‐systolic volume, as well as LV global strain cardiac parameters were measured. Statistical Tests: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all‐cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life‐threatening arrhythmia. Cox proportional‐hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C‐index was computed to examine the prognostic value of VRLN. P‐value <0.05 were considered statistically significant. Results: Participants were followed for a median of 26 months. VRLN, age, LV end‐systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C‐index of the baseline model: 0.781 vs. the model added VRLN: 0.814). Data Conclusion: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. Evidence Level: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

This study revealed that benzyl vinyl ether (BnVE) shows a peculiar isomerization propagation in its radical copolymerization with an electron‐deficient acrylate carrying a pentafluorophenyl group (PFA). The co‐monomer pair inherently exhibits the cross‐over propagation feature due to the large difference in the electron density. However, the radical species of PFA was found to undergo a backward isomerization to the penultimate BnVE pendant giving a benzyl radical species prior to propagation with BnVE. The isomerization brings a drastic change in the character of the growing radical species from electrophilic to nucleophilic, and thus the isomerized benzyl radial species propagates with PFA. Consequently, the two monomers were consumed in the order AAB (A: PFA; B: BnVE) and the unique periodic consumption was confirmed by the pseudo‐reactivity ratios calculated by the penultimate model: r11=0.174 and r21=6600 for PFA (M1) with BnVE (M2). The pentafluorophenyl ester groups of the resulting copolymers are transformed into ester and amide groups by post‐polymerization alcoholysis and aminolysis modifications. The unique isomerization in the AAB sequence allowed the periodic introduction of a benzyl ether structure in the backbone leading to efficient degradation under acid conditions. [ABSTRACT FROM AUTHOR]

Background: During acute health deterioration, emergency medicine and palliative care clinicians routinely discuss code status (e.g., shared decision making about mechanical ventilation) with seriously ill patients. Little is known about their approaches. We sought to elucidate how code status conversations are conducted by emergency medicine and palliative care clinicians and why their approaches are different. Methods: We conducted a sequential‐explanatory, mixed‐method study in three large academic medical centers in the Northeastern United States. Attending physicians and advanced practice providers working in emergency medicine and palliative care were eligible. Among the survey respondents, we purposefully sampled the participants for follow‐up interviews. We collected clinicians' self‐reported approaches in code status conversations and their rationales. A survey with a 5‐point Likert scale ("very unlikely" to "very likely") was used to assess the likelihood of asking about medical procedures (procedure based) and patients' values (value based) during code status conversations, followed by semistructured interviews. Results: Among 272 clinicians approached, 206 completed the survey (a 76% response rate). The reported approaches differed greatly (e.g., 91% of palliative care clinicians reported asking about a patient's acceptable quality of life compared to 59% of emergency medicine clinicians). Of the 206 respondents, 118 (57%) agreed to subsequent interviews; our final number of semistructured interviews included seven emergency medicine clinicians and nine palliative care clinicians. The palliative care clinicians stated that the value‐based questions offer insight into patients' goals, which is necessary for formulating a recommendation. In contrast, emergency medicine clinicians stated that while value‐based questions are useful, they are vague and necessitate extended discussions, which are inappropriate during emergencies. Conclusions: Emergency medicine and palliative care clinicians reported conducting code status conversations differently. The rationales may be shaped by their clinical practices and experiences. [ABSTRACT FROM AUTHOR]

Study Objective: The effects of the sodium‐dependent glucose transporter‐2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub‐analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects. Design: A sub‐analysis of a randomized controlled study. Setting: Chiba University Hospital and ten hospitals in Japan. Patients: Fifteen patients with type 2 diabetes in the ipragliflozin group and 15 patients with type 2 diabetes in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication. Interventions: Ipragliflozin 50 mg or metformin 1000 mg daily. Measurements: The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time‐of‐flight mass spectrometry. Main Results: The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (p = 0.002) in the ipragliflozin group (−19.8%) than in the metformin group (−2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ‐glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low‐density lipoprotein cholesterol levels decreased in the metformin group. After ipragliflozin administration, N2‐phenylacetylglutamine, inosine, guanosine, and 1‐methyladenosine levels increased, whereas galactosamine, glucosamine, 11‐aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl‐2‐oxovaleric acid, 3‐nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole‐3‐acetaldehyde, and hexanoic acid levels decreased. Conclusions: Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Aim: There are few reports on the safety of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) in the elderly. In this study, we investigated the safety of EUS‐FNA for pancreatic solid masses in patients aged ≥80 years. Methods: This is a single‐center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS‐FNA under midazolam‐based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared. Results: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS‐FNA. Conclusions: Our analysis suggests that EUS‐FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836–841. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β3‐adrenoceptor agonist approved for the treatment of overactive bladder. However, how β3‐adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. Methods: In a rat model of Parkinson's disease induced by unilateral 6‐hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. Results: Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter‐contraction interval (p <.05) and reduced voiding pressure (p <.01). However, no significant effects on urethral function were observed. Conclusions: The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β3‐adrenoceptor agonists. [ABSTRACT FROM AUTHOR]

Background: The lymph node metastasis rate in right‐sided colon cancer is unknown, and the optimal central vascular ligation level remains controversial. We aimed to determine the lymph node metastasis rate and short‐term results of radical surgery with extended lymph node dissection in right‐sided colon cancer. Methods: This prospective multicenter observational study included patients with stage II/III right‐sided colon cancer from five cancer hospitals. The metastasis rate of each node station was analyzed according to tumor location and main feeding artery. Results: Between April 2018 and August 2021, 208 patients underwent dissection around the superior mesenteric artery (SMA) and vein (SMV). In transverse colon cancer, 7.5% and 2.5% of metastases occurred around the SMV and SMA at the root of the middle colic artery (MCA), respectively; 6.7% and 6.7% at the root of the right colic artery. In caecal cancer, 1.9% of metastases occurred around the SMV and 1.9% around the SMA. In ascending colon cancer, the rate was 1.1% around the SMV. Of the tumors, 17% fed mainly by the ileocolic artery had node metastases along the middle or right colic artery, as did 66.7% fed mainly by the right colic artery and 41.2% fed by the MCA (p = 0.01). Postoperative complications occurred in 42 patients (20.2%). Conclusion: Routine prophylactic extended lymphadenectomy around the SMA might not be necessary in caecum and ascending colon cancer. Dissection around the SMA may be necessary in cases of transverse colon cancer or when the feeding artery is the MCA. [ABSTRACT FROM AUTHOR]

The craniofacial bones provide structural support for the skull and accommodate the vulnerable brain tissue with a protective cavity. The bone tissue undergoes constant turnover, which relies on skeletal stem cells (SSCs) and/or mesenchymal stem cells (MSCs) and their niches. SSCs/MSCs and their perivascular niche within the bone marrow are well characterized in long bones. As for cranial bones, besides bone marrow, the suture mesenchyme has been identified as a unique niche for SSCs/MSCs of craniofacial bones. However, a comprehensive study of the two different cranial stem cell niches at single‐cell resolution is still lacking. In addition, during the progression of aging, age‐associated changes in cranial stem cell niches and resident cells remain uncovered. In this study, we investigated age‐related changes in cranial stem cell niches via single‐cell RNA sequencing (scRNA‐seq). The transcriptomic profiles and cellular compositions have been delineated, indicating alterations of the cranial bone marrow microenvironment influenced by inflammaging. Moreover, we identified a senescent mesenchymal cell subcluster and several age‐related immune cell subclusters by reclustering and pseudotime trajectory analysis, which might be closely linked to inflammaging. Finally, differentially expressed genes (DEGs) and cell–cell communications were analyzed during aging, revealing potential regulatory factors. Overall, this work highlights the age‐related changes in cranial stem cell niches, which deepens the current understanding of cranial bone and suture biology and may provide therapeutic targets for antiaging and regenerative medicine. [ABSTRACT FROM AUTHOR]

Cranial bones constitute a protective shield for the vulnerable brain tissue, bound together as a rigid entity by unique immovable joints known as sutures. Cranial sutures serve as major growth centres for calvarial morphogenesis and have been identified as a niche for mesenchymal stem cells (MSCs) and/or skeletal stem cells (SSCs) in the craniofacial skeleton. Despite the established dogma of cranial bone and suture biology, technological advancements now allow us to investigate these tissues and structures at unprecedented resolution and embrace multiple novel biological insights. For instance, a decrease or imbalance of representation of SSCs within sutures might underlie craniosynostosis; dural sinuses enable neuroimmune crosstalk and are newly defined as immune hubs; skull bone marrow acts as a myeloid cell reservoir for the meninges and central nervous system (CNS) parenchyma in mediating immune surveillance, etc. In this review, we revisit a growing body of recent studies that explored cranial bone and suture biology using cutting‐edge techniques and have expanded our current understanding of this research field, especially from the perspective of development, homeostasis, injury repair, resident MSCs/SSCs, immunosurveillance at the brain's border, and beyond. [ABSTRACT FROM AUTHOR]

We report syntheses of isotactic polyacrylate and polyacrylamide via a stereospecific radical polymerization of a pendant‐transformable monomer, acrylamide carrying isopropyl‐substituted ureidosulfonamide (1), followed by post‐polymerization modification (PPM). The study in the alcoholysis and aminolysis reactions of the model compound (2) for evaluation of the transformation ability of the electron‐withdrawing pendant group on the repeating unit 1 revealed the following points: the pendant of the polymer became more reactive than that of monomer; the pendant was active enough for aminolysis reaction affording the amide compound quantitatively without additive/catalyst; the addition of a lithium triflate [Li(OTf)] and triethylamine (Et3N) was effective as for promotion of the alcoholysis reaction. Poly(methyl acrylate) (PMA) was quantitatively obtained via the radical polymerization of 1 in the presence of Li(OTf) at 60 °C and the subsequent addition of methanol along with Et3N. Thus‐obtained PMA showed higher isotacticity [m=74 %] than that directly obtained via radical polymerization of methyl acrylate (MA) (m=51 %). The isotacticity was further increased as the temperature and monomer concentration were lower, and eventually m was increased up to 93 %. The aminolysis PPM after the iso‐specific radical polymerization of 1 gave various isotactic polyacrylamides carrying different alkyl pendant groups, including poly(N‐isopropylacrylamide) (PNIPAM). [ABSTRACT FROM AUTHOR]

In this work, we achieved a triggering degradation of polymers composed of carbon‐carbon (C−C) bonded backbone without relying on introduction of labile heteroatom‐based bond. The crucial point for the achievement is using vinyl ether (VE) as a comonomer in radical copolymerization of (meth)acrylate for introduction of the carbon‐hydrogen (C−H) bonds active for photocatalyzed hydrogen atom transfer (HAT) as triggers in the pendant. Interestingly, methyl methacrylate (MMA)‐n‐butyl vinyl ether (NBVE) copolymer underwent degradation in acetonitrile in the presence of benzophenone (Ph2CO) under UV irradiation at 80 °C. The degradation did not take place, when any one of UV, Ph2CO, heat, and NBVE unit was removed or HAT‐active solvent such as toluene and 1,4‐dioxane was used. These control experiments strongly supported the HAT‐triggering degradation. Furthermore, the degradation behaviors of the copolymers with other vinyl ethers such as tert‐butyl vinyl ether and methyl isopropenyl ether indicated that the C−H bond neighboring to oxygen on the pendant is mainly responsible for the trigger leading to degradation. The HAT‐triggering degradation was also demonstrated even with the acrylate‐based copolymer. [ABSTRACT FROM AUTHOR]

The total meridional heat transport (MHT) is relatively stable across different climates. Nevertheless, the strength of individual processes contributing to the total transport are not stable. Here we investigate the MHT and its main components especially in the atmosphere, in five coupled climate model simulations from the Deep‐Time Model Intercomparison Project (DeepMIP). These simulations target the early Eocene climatic optimum, a geological time period with high CO2 concentrations, analog to the upper range of end‐of‐century CO2 projections. Preindustrial and early Eocene simulations, at a range of CO2 levels are used to quantify the MHT changes in response to both CO2 and non‐CO2 related forcings. We found that atmospheric poleward heat transport increases with CO2, while oceanic poleward heat transport decreases. The non‐CO2 boundary conditions cause more MHT toward the South Pole, mainly through an increase in the southward oceanic heat transport. The changes in paleogeography increase the heat transport via transient eddies at the northern mid‐latitudes in the Eocene. The Eocene Hadley cells do not transport more heat poleward, but due to the warmer atmosphere, especially the northern cell, circulate more heat in the tropics, than today. The monsoon systems' poleward latent heat transport increases with rising CO2 concentrations, but this change is counterweighted by the globally smaller Eocene monsoon area. Our results show that the changes in the monsoon systems' latent heat transport is a robust feature of CO2 warming, which is in line with the currently observed precipitation increase of present day monsoon systems. Plain Language Summary: In the Earth's climate system both the atmosphere and the ocean are transporting heat through different processes from the tropics toward the poles. We investigate the transport of the atmosphere in several climate model set ups, which aim to simulate the very warm climate of the early Eocene (∼56–48 Myr ago). This period is relevant, because the atmospheric CO2 concentration was close to our pessimistic projection of CO2 concentration for the end of the century. In our study we separate the results into transport changes due to the different set up of the Eocene, and transport changes due to larger CO2 concentration values. We found that with rising CO2 values the atmosphere transports more heat from the tropics to the poles. The different location of the continents and seas is influencing the heat transport of the midlatitude cyclones. The Eocene tropical meridional overturning circulation's poleward heat transport does not increase, but it circulates more heat than today. The monsoon systems seem to be affecting a globally smaller area in the Eocene, but they are also more effective in transporting heat. This conclusion is in line with the observation, that current day monsoon systems' precipitation increases, as our CO2 concentration rises. Key Points: The latent heat transport of the monsoon increases through the Eocene higher CO2 concentration, but it is reduced by the Eocene topographyThe poleward heat transport of midlatitude cyclones is higher in the Northern Hemisphere in the Eocene, due to the different topographyThe Eocene northern Hadley cell circulates more heat, than in the present, while its net poleward heat transport is even less than today [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia associated with retinal degeneration. The disease is rare in Japan, and this is the first full description of clinicopathological findings in a Japanese autopsy case of genetically confirmed SCA7 having 49 cytosine‐adenine‐guanine (CAG) trinucleotide repeats in the ataxin 7 gene. A 34‐year‐old Japanese man with no family history of clinically apparent neurodegenerative diseases presented with gait disturbance, gradually followed by truncal instability with progressive visual loss by the age of 42 years. He became wheelchair‐dependent by 51 years old, neurologically exhibiting cerebellar ataxia, slow eye movement, slurred and scanning speech, lower limb spasticity, hyperreflexia, action‐related slowly torsional dystonic movements in the trunk and limbs, diminished vibratory sensation in the lower limbs, auditory impairment, and macular degeneration. Brain magnetic resonance imaging revealed atrophy of the brainstem and cerebellum. He died of pneumonia at age 60 with a 26‐year clinical duration of disease. Postmortem neuropathological examination revealed pronounced atrophy of the spinal cord, brainstem, cerebellum, external globus pallidus (GP), and subthalamic nucleus, microscopically showing neuronal cell loss and fibrillary astrogliosis with polyglutamine‐immunoreactive neuronal nuclei and/or neuronal nuclear inclusions (NNIs). Degeneration was also accentuated in the oculomotor system, auditory and visual pathways, upper and lower motor neurons, and somatosensory system, including the spinal dorsal root ganglia. There was a weak negative correlation between the frequency of nuclear polyglutamine‐positive neurons and the extent of neuronal cell loss. Clinicopathological features in the present case suggest that neurological symptoms, such as oculomotor, auditory, visual, and sensory impairments, are attributable to degeneration in their respective projection systems affected by SCA7 pathomechanisms and that dystonic movement is related to more significant degeneration in the external than internal GP. [ABSTRACT FROM AUTHOR]

Aim: Acute chest pain is a commonly encountered symptom in hospital medical/surgical units; however, almost half of nurses in their second year of clinical experience in our facility have reported struggling to care for acute chest pain patients. We developed, implemented, and examined the effectiveness of a simulation‐based, mastery learning clinical nursing educational program to improve self‐efficacy and performance in caring for patients with acute chest pain. Methods: The study adopted a single‐site, single‐cohort design using simulation‐based performance assessment and self‐efficacy surveys on a convenience sample of 37 second‐year clinical nurse participants in multi‐stage hybrid mastery learning educational intervention using asynchronous e‐learning, and hands‐on simulation training and assessment with feedback on caring for chest pain patients. Performance assessments and self‐efficacy surveys were administered pre‐, post‐, and 5 months post‐intervention. Results: Clinical performance on the post‐ and 5 months follow‐up assessments were significantly higher than those for the pre‐test (P <.0001). The self‐efficacy scores for the post‐ and the 5 months follow‐up assessments were significantly higher than the pre‐course scores (P <.0001). Participants' self‐efficacy perceptions were positively correlated with their performances at 5 months post‐intervention. Conclusion: Performance and self‐efficacy of novice nurses in caring for acute chest pain patients improved significantly with the multi‐stage hybrid mastery learning educational intervention, with improvements retained 5 months post‐intervention. The results suggest the applicability of simulation‐based mastery learning in a clinical setting for novice nurses to attain specific skills, and raise their self‐perception of competence to care for patients in acute settings. [ABSTRACT FROM AUTHOR]

In this study, we designed a methacrylate molecule with an alkyl‐substituted trichloro salicylic acid pendant as a transformable bulky monomer to enable the synthesis of an alternating copolymer of methyl methacrylate (MMA) and n‐butyl acrylate (nBA). The adamantyl‐substituted methacrylate monomer (1‐Ad) showed very low homopolymerization propensity in radical polymerizations, but afforded the alternating copolymer with nBA via copolymerization. The 1‐Ad units in the resultant copolymer were quantitatively and selectively transformed into MMA via transesterification with methanol to yield the alternating copolymer of MMA and nBA. Its alternating sequence was clearly demonstrated by a structural analysis via 13C NMR spectroscopy as well as the low reactivity ratios for the 1‐Ad and nBA pair. Finally, we verified the superior self‐healing ability of the alternating copolymer compared to that of the corresponding 1 : 1 statistical copolymer. [ABSTRACT FROM AUTHOR]

Recently, the interface between an organic molecular layer and a topological insulator (TI) surface (Org./TI interface) has been studied to explore the possibility of multifunctional TI devices with organic molecules. Nevertheless, understanding of the electronic structure of Org./TI interfaces is insufficient. Especially, little is known about physisorption systems, where the interaction between adsorbed molecules and topological surface state (TSS) is weak. Here, we discuss an ideal physisorption system of an n‐alkane molecule, n‐tetratertacontane (TTC), and prototypical TI, Bi2Se3, in which the interaction between the molecule and TSS is the weakest one possible. Angle‐resolved photoemission spectroscopy results show that the energy of the Dirac cone (DC) energy band decreases by approximately 60 meV when the TTC layer is formed on Bi2Se3. The amount of energy reduction is consistent with the reduction in vacuum level at the TTC/Bi2Se3 interface, valence states of Bi2Se3 and the core levels of Bi2Se3 observed by ultraviolet‐ and X‐ray photoemission spectroscopy. Therefore, no chemical interactions, such as charge transfer, occur at the TTC/Bi2Se3 interface, but only a redistribution of charge density on the Bi2Se3 surface occurs due to the Pauli repulsion between the electrons of the adsorbed TTC molecule and TSS. [ABSTRACT FROM AUTHOR]

Estimates of global mean near‐surface air temperature (global SAT) for the Cenozoic era rely largely on paleo‐proxy data of deep‐sea temperature (DST), with the assumption that changes in global SAT covary with changes in the global mean deep‐sea temperature (global DST) and global mean sea‐surface temperature (global SST). We tested the validity of this assumption by analyzing the relationship between global SST, SAT, and DST using 25 different model simulations from the Deep‐Time Model Intercomparison Project simulating the early Eocene Climatic Optimum (EECO) with varying CO2 levels. Similar to the modern situation, we find limited spatial variability in DST, indicating that local DST estimates can be regarded as a first order representative of global DST. In line with previously assumed relationships, linear regression analysis indicates that both global DST and SAT respond stronger to changes in atmospheric CO2 than global SST by a similar factor. Consequently, this model‐based analysis validates the assumption that changes in global DST can be used to estimate changes in global SAT during the early Cenozoic. Paleo‐proxy estimates of global DST, SST, and SAT during EECO show the best fit with model simulations with a 1,680 ppm atmospheric CO2 level. This matches paleo‐proxies of EECO atmospheric CO2, indicating a good fit between models and proxy‐data. Plain Language Summary: The global mean surface temperature is a commonly used indicator to measure global climate change. Our understanding of how the global surface temperature has changed in the last 66 Myr is mainly based on the assumption that changes in the deep‐sea temperature (DST) reflect changes at the surface well. Here, we test this idea by using climate model simulations of a hothouse period, the early Eocene Climate Optimum (53–49 Myr ago). We find that changes in the global DST indeed correlate well with temperature changes at the surface. We find the best fit between the models and data from the early Eocene for atmospheric CO2 levels at around 1,680 ppm. Key Points: In early Eocene model simulations (Deep‐Time Model Intercomparison Project [DeepMIP]), global mean deep‐sea, and surface temperatures are equally sensitive to atmospheric CO2 changesModel‐simulated deep‐sea temperatures show limited spatial variability, making local estimates generally representative of the global meanThe model simulations with a CO2 forcing of 1,680 ppm match paleo‐proxies of global mean deep‐sea, sea‐surface, and surface temperature [ABSTRACT FROM AUTHOR]

The development of polymers with on‐demand degradability is required to alleviate the current global issues on polymer‐waste pollution. Therefore, we designed a vinyl ether monomer with an o‐nitrobenzyl (oNBn) group as a photo‐deprotectable pendant (oNBnVE) and synthesized an alternating copolymer with an oNBn‐capped acetal backbone via cationic copolymerization with p‐tolualdehyde (pMeBzA). The resultant alternating copolymer could be rapidly degraded into lower‐molecular‐weight compounds upon simple exposure to UV irradiation without any reactants or catalysts, while it was sufficiently stable toward heat and ambient light. This degradation proceeds via cleavage of the hemiacetal structure generated upon photo‐deprotection of the oNBn pendant. The oNBn‐peculiar degradability allowed the exclusive photo‐degradation of the oNBnVE/pMeBzA segments in a diblock copolymer composed of oNBnVE/pMeBzA and benzyl vinyl ether (BnVE)/pMeBzA segments. [ABSTRACT FROM AUTHOR]

Pemphigus and pemphigoid are autoimmune blistering diseases that affect mucosa and skin. Several clinical scoring systems, including the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), have been validated for managing disease activity and severity. Current guidelines recommend that treatment response be evaluated with clinical scores and that additional second‐line therapies be considered if initial treatment is insufficient for disease control. However, there have been few studies analyzing correlations between PDAI/BPDAI transitions and initial treatment effects. To investigate whether PDAI/BPDAI transitions during the treatment initiation phase correlate with initial treatment responses and whether such information can be used as a guide for necessary additional treatment, we retrospectively analyzed 67 pemphigus patients and 47 pemphigoid patients who received initial treatment at Keio University between 2012 and 2018. The clinical symptoms were evaluated weekly with PDAI/BPDAI. The patients were divided into two groups: in group A, disease was controlled only with oral corticosteroids and immunosuppressants (initial treatment), whereas in group B additional therapies were required due to insufficient responses. In pemphigus, the PDAI ratio of day 7/day 0 was significantly reduced in group A compared to group B (0.548 vs 0.761, P < 0.01) after initial treatment had started. In pemphigoid, the ratios of day 7/day 0 of BPDAI (erosion/blister) and BPDAI (urticaria/erythema) significantly decreased in group A compared to group B (0.565 vs 0.901 and 0.350 vs 0.760, respectively, P < 0.05). Receiver operating characteristic analyses on PDAI, BPDAI (erosion/blister) and BPDAI (urticaria/erythema) revealed that the cut‐off values in the ratios of day 7/day 0 were 0.762, 0.675, and 0.568, respectively. Our results suggest that PDAI/BPDAI transitions during the initial phase of the treatments may be useful to predict the outcome of the treatment provided and the necessity of additional therapies to achieve disease control. [ABSTRACT FROM AUTHOR]

Abnormal lightening of the oxygen isotope ratio (δ18O) of planktonic foraminifera during the Last Glacial Maximum (LGM, ∼21 kyr BP) suggests that the Japan Sea had experienced a low sea surface salinity event at that time. However, the exact value and timing of minimum salinity have been controversial so far. To address this issue, we adopt a simple box model and reconstruct the sea surface salinity in the Japan Sea (SJP) over the past 35 kyr with a focus on the LGM period. In particular, as input data for the box model, the inflow transport through the Tsushima Strait (Q) is converted from sea level evolution using a newly defined relationship, in which Q reduces non‐linearly with the sea level reduction through a dynamically‐constrained realistic ocean model. Meanwhile, another input data of the box model, sea surface freshwater flux (precipitation minus evaporation (P‐E) evolution), is obtained by averaging multi‐paleoclimate models (PMIP3 and MIROC4m models) results. The reconstructed SJP using the box model reached its minimum value (20.2) at 20 kyr BP with a high coefficient of determination (R2) for δ18O (0.81, p << 0.01). Further analysis demonstrates that the above non‐linear relationship, determined by h3/2 (h is the strait depth), promises a more reasonable reconstruction of the SJP evolution. It is also concluded that both the value and timing of the minimum SJP depend on the Q evolution, and the P‐E evolution can modify the former. Therefore, the combination of Q and P‐E determines the exact value and timing of minimum salinity. Plain Language Summary: Twenty one thousand years ago, as a large volume of water froze over land at the Last Glacial Maximum (LGM), the global sea level was depressed by about 130 m. Some semi‐enclosed marginal seas with shallow entrances, like the Japan Sea, became completely or almost isolated. Limited communication with the surrounding seas and continuous freshwater input led to a low surface salinity event in the Japan Sea. With two refinements on prior reconstructions of surface salinity, we configure a simple box model to obtain its minimum value (20.2) at 20 kyr BP. Among two refinements, one is a nonlinear‐constrained evolution of the inflow transport through the Tsushima Strait; the other is a more reasonable evolution of freshwater flux from multi‐paleoclimate models. The reduction of surface salinity could enhance the density stratification and severely restrict the deep convection, leaving a poorly‐ventilated, anoxic, and sulfidic deep water, which has been suggested for the environment in the Japan Sea during the LGM. It is noted that such box models can be applied to other semi‐enclosed marginal seas. Key Points: Volume transport through the Tsushima Strait reduces non‐linearly when the sea level reduces linearlySea surface salinity of the Japan Sea reached its minimum value (20.2) at 20 kyr BPVolume transport through the Tsushima Strait dominates the value and timing of the minimum salinity, and P‐E can modify the former [ABSTRACT FROM AUTHOR]

We first prove semi‐orthogonal decompositions of derived factorization categories arising from sums of potentials of gauged Landau–Ginzburg models, where the sums are not necessarily Thom–Sebastiani type. We then apply the result to the category HMFLf(f)$\operatorname{HMF}^{L_f}(f)$ of maximally graded matrix factorizations of an invertible polynomial f$f$ of chain type, and explicitly construct a full strong exceptional collection E1,⋯,Eμ$E_1,\hdots ,E_{\mu }$ in HMFLf(f)$\operatorname{HMF}^{L_f}(f)$ whose length μ$\mu$ is the Milnor number of the Berglund–Hübsch transpose f∼$\widetilde{f}$ of f$f$. This proves a conjecture, which postulates that for an invertible polynomial f$f$ the category HMFLf(f)$\operatorname{HMF}^{L_f}(f)$ admits a tilting object, in the case when f$f$ is a chain polynomial. Moreover, by careful analysis of morphisms between the exceptional objects Ei$E_i$, we explicitly determine the quiver with relations (Q,I)$(Q,I)$ which represents the endomorphism ring of the associated tilting object ⊕i=1μEi$\oplus _{i=1}^{\mu }E_i$ in HMFLf(f)$\operatorname{HMF}^{L_f}(f)$, and in particular we obtain an equivalence HMFLf(f)≅Db(modkQ/I)$\operatorname{HMF}^{L_f}(f)\cong \operatorname{D}^{\operatorname{b}}(\operatorname{mod}kQ/I)$. [ABSTRACT FROM AUTHOR]

Background: During the mixed dentition period, masticatory performance may temporarily decline as deciduous teeth are replaced by permanent teeth. This may lead to an insufficient intake of chewy foods. Objectives: This study aimed to clarify the characteristics of factors that affect masticatory performance during the dentition exchange period. Methods: The participants were 229 students in grades 4–6 who were in the lateral dentition exchange period. Shearing performance (SP) was evaluated using gummy jelly, and mixing performance (MP) was evaluated using colour‐changing gum. The chewing rate, occlusal force and area, number of teeth, Hellman's tooth age, Rohrer index, grip strength and walking speed were also evaluated. The χ2 test, Mann–Whitney test, Spearman's rank correlation coefficient and a generalised linear model were used for statistical analysis. Results: SP/MP showed a significant positive correlation with occlusal force, occlusal contact area and chewing rate for gummy jelly and gum but there was a difference in the strength of the correlation between boys and girls. Chewing rate for gummy jelly and gum showed a significant relationship with both SP and MP, suggesting that masticatory performance is higher with slower chewing. Maximum occlusal force was selected as a significant independent variable for SP, and Rohrer index was selected as a significant independent variable for MP. When the occlusal force was higher and the Rohrer index was lower, the masticatory performance tended to be higher. Conclusions: Our results suggest that masticatory performance during the dentition exchange period is higher with slower chewing and a stronger occlusal force, which may be related to obesity. [ABSTRACT FROM AUTHOR]

The article is a response to a study on the efficacy of physiotherapy in post-prostatectomy continence and pelvic muscle function. The authors address concerns raised by Tang et al. regarding preoperative patient history and treatments besides pelvic floor muscle training. The study found no significant differences in residual urine volume between the groups, indicating that this characteristic did not impact the analysis. The authors declare no competing interests, and the study focused on evaluating the effectiveness of supervised pelvic floor muscle training on continence and muscle function. [Extracted from the article]

Inconsistencies in the Eocene climates of East Asia have been revealed in both geological studies and simulations. Several earlier reconstructions showed an arid zonal band in mid‐latitude China, but others showed a humid climate in the same region. Moreover, previous Eocene modeling studies have demonstrated that climate models can simulate both scenarios in China. Therefore, it is essential to investigate the cause of this model spread. We conducted a series of experiments using Norwegian Earth System Model 1‐F and examined the impact of mountains in Southern China on the simulated Eocene climate. These mountains, including the Gangdese and Southeast Mountains, are located along the main path of water vapor transport to East Asia. Our results reveal that the Southeast Mountains play the dominant role in controlling the simulated precipitation in Eastern China during the Eocene. When the heights of the Southeast Mountains exceed ∼2,000 m, an arid zonal band appears in mid‐latitude China, whereas humid climates appear in Eastern China when the elevation of the Southeast Mountains is relatively low. Key Points: Southeast Mountains control simulated Eocene precipitation in Eastern ChinaWhen the Southeast Mountains are high, an arid zonal band appears in mid‐latitude ChinaThe early Eocene climate in East Asia is not monsoonal climate [ABSTRACT FROM AUTHOR]

The cetuximab gene expression signature and DNA methylation status of colorectal cancer (CRC) are predictive of the therapeutic effects of anti‐epidermal growth factor receptor (EGFR) antibody therapy. As DNA methylation is a means of regulating gene expression, it may play an important role in the expression of cetuximab signature genes. This study aims to determine the effects of aberrant DNA methylation on the regulation of cetuximab signature gene expression. Comprehensive DNA methylation and gene expression data were retrieved from CRC patients in three tumor tissue (TT) cohorts and three normal colorectal mucosa/tumor tissue paired (NCM‐TT) cohorts. Of the 231 cetuximab signature genes, 57 exhibited an inverse correlation between the methylation of promoter CpG sites and gene expression level in multiple cohorts. About two‐thirds of the promoter CpG sites associated with the 57 genes exhibited this correlation. In all 57 gene promoter regions, the methylation levels in NCMs did not differ according to comparisons based on cetuximab signature or DNA methylation status classification of matched TTs. Thus, the altered expression of 57 genes was caused by aberrant DNA methylation during carcinogenesis. Analysis of the association between cetuximab signature or DNA methylation status and progression‐free survival (PFS) of anti‐EGFR antibody agents in the same cohort showed that DNA methylation status was most associated with PFS. In conclusion, we found that aberrant DNA methylation regulates specific gene expression in cetuximab signature during carcinogenesis, suggesting that it is one of the important determinants of sensitivity to anti‐EGFR antibody agents. [ABSTRACT FROM AUTHOR]

We report the first total synthesis of isosilybin B (4). Our synthetic strategy features the modified Julia‐Kocienski olefination reaction developed in our laboratory between m‐NPT sulfone 19 and aldehyde 27, the construction of benzodihydropyran 34 via formation of a quinomethide intermediate under acidic conditions and the oxidation of benzodihydropyran to flavanonol 37. [ABSTRACT FROM AUTHOR]

Aims: Data on B‐type natriuretic peptide (BNP) levels and adverse outcomes in patients with moderate mixed aortic valve disease (MAVD), defined as moderate aortic stenosis (AS) and regurgitation (AR), are scarce. Therefore, this study investigated the impact of BNP on the clinical outcomes in such patients. Methods and results: Clinical data from 81 patients (mean age, 74.1 ± 6.8 years; 50.6%, men) treated for moderate MAVD and left ventricular ejection fraction (LVEF) ≥ 50% during 2010–2018 were retrospectively analysed. Specific echocardiographic data of the study patients were LVEF of 57.8 ± 5.0%, aortic valve index of 0.64 ± 0.04 cm2/m2, peak aortic valve velocity of 3.38 ± 0.29 m/s, and AR vena contracta width of 4.2 ± 0.7 mm. The median BNP level was 61.4 pg/mL (interquartile range, 29.7–109.9). The primary endpoint was a composite of all‐cause death, heart failure hospitalization, and aortic valve replacement, and its cumulative incidence at 5 years was 57.7%. Multivariable analysis revealed that age (hazard ratio, 1.079; 95% confidence interval, 1.028–1.133; P = 0.002) and BNP levels (hazard ratio, 1.028; 95% confidence interval, 1.003–1.053; P = 0.027) were significantly related to the endpoint; specifically, BNP > 61.4 pg/mL had significantly higher incidence rates of the endpoint than those with a BNP ≤ 61.4 pg/mL (70.3% vs. 45.5% at 5 years; P = 0.018). Compared with patients with BNP ≤ 61.4 pg/mL, those with BNP > 61.4 pg/mL had significantly worse left ventricular global longitudinal strain (−17.1 ± 3.6% vs. −18.7 ± 2.6%; P = 0.029), along with higher left ventricular mass index (116.9 ± 27.8 g/m2 vs. 103.5 ± 19.7 g/m2; P = 0.014), relative wall thickness (0.45 ± 0.07 vs. 0.42 ± 0.05; P = 0.022), left atrial volume index (46.0 ± 28.4 mL/m2 vs. 31.4 ± 10.3 mL/m2; P = 0.003), pulmonary artery systolic pressure (32.6 ± 9.7 mmHg vs. 28.2 ± 4.7 mmHg; P = 0.011), and prevalence of moderate or greater tricuspid regurgitation (15.0% vs. 0.0%; P = 0.012). Conclusions: Patients with moderate MAVD are at higher risk of unfavourable clinical outcomes, and age and BNP are independently related to the occurrence of adverse events. High BNP levels may reflect extravalvular cardiac damage in patients with moderate MAVD. [ABSTRACT FROM AUTHOR]

Background: The intersection of emergency medicine (EM) and palliative care (PC) has been recognized as an essential area of focus, with evidence suggesting that increased integration improves outcomes. This has resulted in increased research in EM PC. No current framework exists to help guide investigation and innovation. Objective: The objective was to convene a working group to develop a roadmap that would help provide focus and prioritization for future research. Methods: Participants were identified based on clinical, operation, policy, and research expertise in both EM and PC and spanned physician, nursing, social work, and patient perspectives. The research roadmap setting process consisted of three distinct phases that were time staggered over 12 months and facilitated through three live video convenings, asynchronous input via an online document, and a series of smaller video convenings of work groups focused on specific topics. Results: Gaps in the literature were identified and informed the four key areas for future research. Consensus was reached on these domains and the associated research questions in each domain to help guide future study. The key domains included work focused on the value imperative for PC in the emergency setting, models of care delivery, disparities, and measurement of impact and efficacy. Additionally, the group identified key methodological considerations for doing work at the intersection of EM and PC. Conclusions: There are several key domains and associated questions that can help guide future research in ED PC. Focus on these areas, and answering these questions, offers the potential to improve the emergency care of patients with PC needs. [ABSTRACT FROM AUTHOR]

Aim: The fetal sample used for embryonic chromosome analysis is often contaminated with maternal cells, making it difficult to evaluate the fetal chromosomes. We examined on the rate of maternal cell contamination and its relationship with maternal information in the embryonic chromosome analysis of missed abortions using the Giemsabanding method. Methods: Chromosome analysis was performed in 200 cases of delayed miscarriages in first trimester between July 1, 2000 and May 31, 2019. Chorionic villi were collected and were analyzed using the Giemsa banding method. Among the 20 cells for which chromosomal examination was performed, cells wherein 46,XX chromosomes were found together with normal male karyotype or abnormal chromosomes were defined as maternal cell contamination. Results: Of the 200 cases analyzed, 136 had abnormal chromosomes. The normal female karyotype (n = 52) was four times more prevalent than the normal male karyotype (n = 12). Maternal cell contamination was seen in 15.4% of the abnormal chromosome cases and 8.3% of the normal male karyotype cases. There was no significant difference in the gestational age between the contaminated and noncontaminated groups at the time of miscarriage diagnosis. However, miscarriage before fetal heartbeat confirmation was significantly associated with higher maternal cell contamination. Conclusion: We found maternal cell contamination in 15% of all the cases. Moreover, in many cases of the normal female karyotype, it was suspected that only maternal chromosomes were cultured. When performing embryonic chromosome analysis in recurrent miscarriages, we should pay attention to maternal cell contamination and interpret the results accordingly. [ABSTRACT FROM AUTHOR]

In this paper, the copolymerization of saccharin methacrylamide (1) with conjugated dienes [2,3‐dimethyl butadiene (DMBD) and isoprene (IP)] as comonomers toward advanced sequence control is studied. Both monomers are consumed at the same rate in the copolymerization despite the lack of homopolymerization ability of 1, indicating that the alternating copolymerization likely progresses. The resultant copolymers are transformed into methyl methacrylate (MMA)‐diene alternating copolymers via direct methanolysis reaction for the copolymerization solution. The alternating sequence is characterized by NMR analyses in comparison with the corresponding statistical copolymers. As for the copolymer with IP, the remaining carboncarbon double bonds are hydrogenated for the synthesis of advanced sequence‐controlled polymer, MMA‐(propylene‐ethylene) alternating‐copolymer. [ABSTRACT FROM AUTHOR]

Aim: MATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease. Methods: We administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t‐scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups. Results: Compared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem‐solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition. Conclusions: The Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice. [ABSTRACT FROM AUTHOR]

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography‐derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR‐based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD. [ABSTRACT FROM AUTHOR]

Background and purpose: Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study was to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggregation or glucose metabolism and brain atrophy in patients with mild AD using positron emission tomography (PET). Methods: Amyloid‐ and tau‐positive symptomatic AD patients with clinical dementia rating 0.5 or 1 (N = 30; mean age ± standard deviation: 71.8 ± 7.6 years) underwent magnetic resonance imaging and PET scans with [18F]2‐tert‐butyl‐4‐chloro‐5–2H‐pyridazin‐3‐one (BCPP‐EF), [11C]Pittsburgh Compound‐B (PiB) and [18F]fluorodeoxyglucose (FDG) to assess brain atrophy, mitochondrial complex I dysfunction, amyloid deposition, and glucose metabolism, respectively. Local cortical associations among these biomarkers and gray matter volume were evaluated with voxel‐based regressions models. Results: [18F]BCPP‐EF standardized uptake value ratio (SUVR) was positively correlated with [18F]FDG SUVR in the widespread brain area, while its associations with gray matter volume were restricted to the parahippocampal gyrus. Reductions in [18F]BCPP‐EF SUVR were associated with domain‐specific cognitive performance. We did not observe regional associations between mitochondrial dysfunction and amyloid burden. Conclusions: In symptomatic cases, although mitochondrial complex I reduction is linked to a wide range of downstream neurodegenerative processes such as hypometabolism, atrophy, and cognitive decline, a link to amyloid was not observable. The data presented here support [18F]BCPP‐EF as an excellent imaging tool to investigate mitochondrial dysfunction in AD. [ABSTRACT FROM AUTHOR]