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Objectives: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH. Methods: C57BL/6J mice received a single intraperitoneal injection of 0.5mL of pristane. Neutrophil NLRP3 inflammasome assembly and NETs were characterized by immunofluorescence staining of apoptosis-associated speck-like protein a CARD (ASC), co-staining of DNA, and citrullinated histones, respectively. Clinical status of mice was assessed 11 days after pristane injection by measurement of arterial oxygen saturation and of weight loss; severity of lung injury was determined using a quantification score from hematoxylin-eosin-stained slides. Results: Pristane induced ASC speck formation in neutrophils and we confirmed that NLRP3 inflammasome was involved in NET generation after pristane stimulation in vitro. NLRP3 deficiency reduced the severity of pristane-induced DAH in female, but not male mice. Interestingly, NLRP3 deficiency reduced the number of neutrophils and NETs in the lungs of females compared to males. Conclusions: Our results suggest a link between female sex-specific NLRP3 inflammasome activation and subsequent pulmonary NETosis in the development of pristane-induced DAH. Therefore, we identified NLRP3 inflammasome as a potential new therapeutic target in this severe complication of pro-female autoimmune disease for which specific inhibitors of NLRP3 are currently developed. [ABSTRACT FROM AUTHOR]

The article discusses the use of AI chatbots in education and its potential impact on liberal education. It highlights concerns that AI chatbots may homogenize students' thinking and presentation of ideas, discourage engagement with valuable learning processes, and prioritize performance over effort. The author suggests that the use of AI chatbots in education should be accompanied by a redesign of assessment methods and a shift towards an education system that values learning over grades. The article acknowledges the benefits of AI chatbots for productivity but emphasizes the need to balance these benefits with the preservation of individuality and diversity in education. [Extracted from the article]

Huntington's disease (HD) arises from expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. The resultant misfolded HTT protein accumulates within neuronal cells, negatively impacting their function and survival. Ultimately, HTT accumulation results in cell death, causing the development of HD. A nonhuman primate (NHP) HD model would provide important insight into disease development and the generation of novel therapies due to their genetic and physiological similarity to humans. For this purpose, we tested CRISPR/Cas9 and a single-stranded DNA (ssDNA) containing expanded CAG repeats in introducing an expanded CAG repeat into the HTT gene in rhesus macaque embryos. Analyses were conducted on arrested embryos and trophectoderm (TE) cells biopsied from blastocysts to assess the insertion of the ssDNA into the HTT gene. Genotyping results demonstrated that 15% of the embryos carried an expanded CAG repeat. The integration of an expanded CAG repeat region was successfully identified in five blastocysts, which were cryopreserved for NHP HD animal production. Some off-target events were observed in biopsies from the cryopreserved blastocysts. NHP embryos were successfully produced, which will help to establish an NHP HD model and, ultimately, may serve as a vital tool for better understanding HD's pathology and developing novel treatments. [ABSTRACT FROM AUTHOR]

Many graph polynomials may be derived from the coefficients of the chromatic symmetric function XG ${X}_{G}$ of a graph G $G$ when expressed in different bases. For instance, the chromatic polynomial is obtained by mapping pn→x ${p}_{n}\to x$ for each n $n$ in this function, while a polynomial whose coefficients enumerate acyclic orientations is obtained by mapping en→x ${e}_{n}\to x$ for each n $n$. In this paper, we study a new polynomial we call the tree polynomial arising by mapping XPn→x ${X}_{{P}_{n}}\to x$, where XPn ${X}_{{P}_{n}}$ is the chromatic symmetric function of a path with n $n$ vertices. In particular, we show that this polynomial has a deletion‐contraction relation and has properties closely related to the chromatic polynomial while having coefficients that enumerate certain spanning trees and edge cutsets. [ABSTRACT FROM AUTHOR]

Assume $\mathsf {ZF} + \mathsf {AD}$ and all sets of reals are Suslin. Let $\Gamma $ be a pointclass closed under $\wedge $ , $\vee $ , $\forall ^{\mathbb {R}}$ , continuous substitution, and has the scale property. Let $\kappa = \delta (\Gamma)$ be the supremum of the length of prewellorderings on $\mathbb {R}$ which belong to $\Delta = \Gamma \cap \check \Gamma $. Let $\mathsf {club}$ denote the collection of club subsets of $\kappa $. Then the countable length everywhere club uniformization holds for $\kappa $ : For every relation $R \subseteq {}^{ with the property that for all $\ell \in {}^{ and clubs $C \subseteq D \subseteq \kappa $ , $R(\ell ,D)$ implies $R(\ell ,C)$ , there is a uniformization function $\Lambda : \mathrm {dom}(R) \rightarrow \mathsf {club}$ with the property that for all $\ell \in \mathrm {dom}(R)$ , $R(\ell ,\Lambda (\ell))$. In particular, under these assumptions, for all $n \in \omega $ , $\boldsymbol {\delta }^1_{2n + 1}$ satisfies the countable length everywhere club uniformization. [ABSTRACT FROM AUTHOR]

Assume Z F + A D. If is an ordinal and X is a set of ordinals, then [ X ] ∗ is the collection of order-preserving functions f : → X which have uniform cofinality ω and discontinuous everywhere. The weak partition properties on ω 1 and ω 2 yield partition measures on [ ω 1 ] ∗ when < ω 1 and [ ω 2 ] ∗ when < ω 2 . The following almost everywhere continuity properties for functions on partition spaces with respect to these partition measures will be shown. For every < ω 1 and function Φ : [ ω 1 ] → ω 1 , there is a club C ⊆ ω 1 and a ζ < so that for all f , g ∈ [ C ] ∗ , if f ↾ ζ = g ↾ ζ and sup (f) = sup (g) , then Φ (f) = Φ (g). For every < ω 2 and function Φ : [ ω 2 ] → ω 2 , there is an ω -club C ⊆ ω 2 and a ζ < so that for all f , g ∈ [ C ] ∗ , if f ↾ ζ = g ↾ ζ and sup (f) = sup (g) , then Φ (f) = Φ (g). The previous two continuity results will be used to distinguish the cardinalities of some important subsets of (ω 2) : | [ ω 1 ] ω | < | [ ω 1 ] < ω 1 |. | [ ω 2 ] ω | < | [ ω 2 ] < ω 1 | < | [ ω 2 ] ω 1 | < | [ ω 2 ] < ω 2 |. ¬ (| [ ω 1 ] < ω 1 | ≤ | [ ω 2 ] ω |). ¬ (| [ ω 1 ] ω 1 | ≤ | [ ω 2 ] < ω 1 |). It will also be shown that [ ω 1 ] ω has the Jónsson property: For every Φ : < ω ([ ω 1 ] ω) → [ ω 1 ] ω , there is an X ⊆ [ ω 1 ] ω with | X | = | [ ω 1 ] ω | so that Φ [ < ω X ] ≠ [ ω 1 ] ω . [ABSTRACT FROM AUTHOR]

Background: Undifferentiated carcinomas of the pancreas with osteoclast-like giant cells (UCPOGC) are rare pancreatic neoplasms that account for less than 1% of all pancreatic malignancies. This case report of a 54-year-old male with metastatic UCPOGC adds to the existing literature and further ascertains the clinical and imaging features, treatment options, and prognosis of this rare entity. Case presentation: We present the detailed clinical course of a 54-year-old Asian male patient with UCPOGC, with focus on the relevant clinical features and imaging findings that are characteristic of this disease entity. Conclusions: UCPOGC is an extremely rare pancreatic tumor with a unique histopathology and clinical course. It is often difficult to distinguish UCPOGCs from other pancreatic tumors, such as traditional pancreatic ductal adenocarcinomas (PDAC), on imaging, and it therefore remains a pathological diagnosis. Surgery is generally regarded as the first-line treatment option, and the roles of chemotherapy and radiation are unclear. Due to the exceeding rarity of this tumor, large-scale clinical studies are not feasible. Therefore, it is important to share individual insights and experiences to improve our understanding and care for patients with this devastating disease. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a substrate protein of a Cullin 4B E3 ligase complex responsible for diverse cellular processes. In the lung, this receptor is responsible for the bioactivation of benzo[a]pyrene during tumorigenesis. Realizing that the AHR function is affected by its expression level, we are interested in the degradation mechanism of AHR in the lung. Here, we have investigated the mechanism responsible for AHR degradation using human lung epithelial A549 cells. We have observed that the AHR protein levels increase in the presence of chloroquine (CQ), an autophagy inhibitor, in a dose-dependent manner. Treatment with 6-aminonicotinamide (6-AN), a chaperone-mediated autophagy (CMA) activator, decreases AHR protein levels in a concentration-dependent and time-dependent manner. This decrease suppresses the ligand-dependent activation of the AHR target gene transcription, and can be reversed by CQ but not MG132. Knockdown of lysosome-associated membrane protein 2 (LAMP2), but not autophagy-related 5 (ATG5), suppresses the chloroquine-mediated increase in the AHR protein. AHR is resistant to CMA when its CMA motif is mutated. Suppression of the epithelial-to-mesenchymal transition in A549 cells is observed when the AHR gene is knocked out or the AHR protein level is reduced by 6-AN. Collectively, we have provided evidence supporting that AHR is continuously undergoing CMA and activation of CMA suppresses the AHR function in A549 cells. [ABSTRACT FROM AUTHOR]

Edna Bonacich's split labour market states that socio-political factors generate differential outcomes for workers in a region, generally as the result of ethnic antagonism. This ethnic antagonism, Bonacich argues, does not require open violence or even verbal confrontation but can operate through exclusion movements and "caste" systems. In this paper, we use Bonacich's framework to analyse the production of a split labour market in the Macao, Special Administrative Region of China. Macao depends on an abundant supply of low-skilled migrant workers to remunerate the workforce. While many migrant workers are foreigners, most are 'internal' migrants from Mainland China, meaning that a conventional explanation of ethnic differences is insufficient. Bonacich had observed that "exclusion attempts and caste-like arrangements are found among national groupings within a racial category" giving the example of 'whites' in the United States excluding other 'whites' from different parts of Europe. However, Macao as a part of China constitutes a unique example in that an exclusion attempt and caste-like arrangement is to be found within the same national grouping of the same racial category in the same country. As this research considers how ethnic and quasi-ethnic differences are produced and sustained in Macao through government policy; social attitudes and the social practices of workers and businesses, we find that permanent Macao ID card holders, which gives out numerous benefits and rights, is as a form of exclusion movement. Moreover, local workers act as a labour aristocracy: they extract concessions from businesses and suppress migrant workers economically, politically and socially. Edna Bonacich's split labour market helps explain how a labour aristocracy is maintained subtly at the interest of local workers through concessions from the businesses. [ABSTRACT FROM AUTHOR]

Introduction: Hip fractures in elderly people are increasing. A five-year Integrated Hip Fracture Care Pathway (IHFCP) was implemented at our hospital for seamlessly integrating care for these patients from admission to post discharge. We aimed to evaluate how IHFCP improved process and outcome measures in these patients.Methods: A study was conducted over a five-year period on patients with acute fragility hip fracture who were managed on IHFCP. The evaluation utilised a descriptive design, with outcomes analysed separately for each of the five years of the programme. First-year results were treated as baseline.Results: The main improvements in process and outcome measures over five years, when compared to baseline, were: (a) increase in surgeries performed within 48 hours of admission from 32.5% to 80.1%; (b) reduced non-operated patients from 19.6% to 11.9%; (c) reduced average length of stay at acute hospital among surgically (from 14.0 ± 12.3 days to 9.9 ± 1.0 days) and conservatively managed patients (from 19.1 ± 22.9 to 11.0 ± 2.5 days); (d) reduced 30-day readmission rate from 3.2% to 1.6%; and (e) improved Modified Functional Assessment Classification of VI to VII at six months from 48.0% to 78.2%.Conclusion: The IHFCP is a standardised care path that can reduce time to surgery, average length of stay and readmission rates. It is distinct from other orthogeriatric care models, with its ability to provide optimal care coordination, early transfer to community hospitals and post-discharge day rehabilitation services. Consequently, it helped to optimise patients' functional status and improved their overall outcome. [ABSTRACT FROM AUTHOR]

Objective: Sex differences in patients presenting with out‐of‐hospital cardiac arrest (OHCA) and shockable rhythm might be associated with disparities in clinical outcomes. Methods: We conducted a retrospective cohort study and compared characteristics and short‐term outcomes between male and female adult patients who presented with OHCA and shockable rhythm at two large metropolitan health services in Melbourne, Australia between the period of 2014–2018. Logistic regression was used to assess the effect of sex on clinical outcomes. Results: Of 212 patients, 166 (78%) were males and 46 (22%) were females. Both males and females presented with similar rates of ST‐elevation myocardial infarction (44% vs 36%, P = 0.29), although males were more likely to have a history of coronary artery disease (32% vs 13%) and a final diagnosis of a cardiac cause for their OHCA (89% vs 72%), both P = 0.01. Rates of coronary angiography (81% vs 71%, P = 0.23) and percutaneous coronary intervention (51% vs 42%, P = 0.37) were comparable among males and females. No differences in rates of in‐hospital mortality (38% vs 37%, P = 0.90) and 30‐day major adverse cardiac and cerebrovascular events (composite of all‐cause mortality, myocardial infarction, coronary revascularization and nonfatal stroke) (39% vs 41%, P = 0.79) were observed between males and females, respectively. Female sex was not associated with worse in‐hospital mortality when adjusted for other variables (odds ratio 0.66, 95% confidence interval 0.28–1.60, P = 0.36). Conclusion: Among patients presenting with OHCA and a shockable rhythm, baseline sex and sex differences were not associated with disparities in short‐term outcomes in contemporary systems of care. [ABSTRACT FROM AUTHOR]

BACKGROUND The impact of age on outcomes in cardiogenic shock (CS) is poorly described in the pre-hospital setting. We assessed the impact of age on outcomes of patients treated by emergency medical services (EMS). METHODS This population-based cohort study included consecutive adult patients with CS transported to hospital by EMS. Successfully linked patients were stratified into tertiles by age (18-63, 64-77, and > 77 years). Predictors of 30-day mortality were assessed through regression analyses. The primary outcome was 30-day all-cause mortality. RESULTS A total of 3523 patients with CS were successfully linked to state health records. The average age was 68 ± 16 years and 1398 (40%) were female. Older patients were more likely to have comorbidities including pre-existing coronary artery disease, hypertension, dyslipidemia, diabetes mellitus, and cerebrovascular disease. The incidence of CS was significantly greater with increasing age (incidence rate per 100,000 person years 6.47 [95% CI: 6.1-6.8] in age 18-63 years, 34.34 [32.4-36.4] in age 64-77 years, 74.87 [70.6-79.3] in age > 77 years, P < 0.001). There was a step-wise increase in the rate of 30-day mortality with increasing age tertile. After adjustment, compared to the lowest age tertile, patients aged > 77 years had increased risk of 30-day mortality (adjusted hazard ratio = 2.26 [95% CI: 1.96-2.60]). Older patients were less likely to receive inpatient coronary angiography. CONCLUSION Older patients with EMS-treated CS have significantly higher rates of short-term mortality. The reduced rates of invasive interventions in older patients underscore the need for further development of systems of care to improve outcomes for this patient group. [ABSTRACT FROM AUTHOR]

Background: Patient factors, such as sex and body mass index (BMI), are known to influence patient radiation exposure. Body surface area (BSA) and its association with patient radiation exposure has not been well studied. Methods and Results: We analysed height, weight, BMI and BSA in consecutive patients undergoing cardiac catheterisation and percutaneous coronary intervention (PCI) at a high-volume Australian centre between September 2016 and April 2020 to assess their association with dose–area product (DAP, Gycm2). The mean age of the cohort was 64.5 ± 12.3 years with males comprising 68.8% (n = 8100, 5124 diagnostic cardiac catheterisation cases and 2976 PCI cases). Median male BMI was 28.4 kg/m2 [IQR 25.2–32.1] versus 28.8 kg/m2 [24.7–33.7] for females, p = 0.01. Males had higher BSA (2.0 ± 0.2 m2) than females (1.78 ± 0.2 m2), p = 0.001. Each 0.4 m2 increase in BSA conferred a 1.32x fold change in DAP (95% CI 1.29–1.36, p ≤ 0.001). Each 5 kg/m2 increase in BMI was linked to a 1.13x DAP fold change (1.12–1.14, p ≤ 0.001). Male sex conferred a 1.23x DAP fold change (1.20–1.26, p ≤ 0.001). Multivariable modelling with BMI or BSA explained 14% of DAP variance (R2 0.67 vs. 0.53 for both, p ≤ 0.001). Conclusions: BSA is an important anthropometric measure between the sexes and a key predictor of radiation dose and radiation exposure beyond sex, BMI, and weight. [ABSTRACT FROM AUTHOR]

Objectives: Despite an increase in the use of mechanical circulatory support (MCS) devices for acute myocardial infarction cardiogenic shock (AMI-CS), there is currently no randomised data directly comparing the use of Impella and veno-arterial extra-corporeal membrane oxygenation (VA-ECMO). Methods: Electronic databases of MEDLINE, EMBASE and CENTRAL were systematically searched in November 2021. Studies directly comparing the use of Impella (CP, 2.5 or 5.0) with VA-ECMO for AMI-CS were included. Studies examining other modalities of MCS, or other causes of cardiogenic shock, were excluded. The primary outcome was in-hospital mortality. Results: No randomised trials comparing VA-ECMO to Impella in patients with AMI-CS were identified. Six cohort studies (five retrospective and one prospective) were included for systematic review. All studies, including 7093 patients, were included in meta-analysis. Five studies reported in-hospital mortality, which, when pooled, was 42.4% in the Impella group versus 50.1% in the VA-ECMO group. Impella support for AMI-CS was associated with an 11% relative risk reduction in in-hospital mortality compared to VA-ECMO (risk ratio 0.89; 95% CI 0.83–0.96, I2 0%). Of the six studies, three studies also adjusted outcome measures via propensity-score matching with reported reductions in in-hospital mortality with Impella compared to VA-ECMO (risk ratio 0.72; 95% CI 0.59–0.86, I2 35%). Pooled analysis of five studies with 6- or 12-month mortality data reported a 14% risk reduction with Impella over the medium-to-long-term (risk ratio 0.86; 95% CI 0.76–0.97, I2 0%). Conclusions: There is no high-level evidence comparing VA-ECMO and Impella in AMI-CS. In available observation studies, MCS with Impella was associated with a reduced risk of in-hospital and medium-term mortality as compared to VA-ECMO. [ABSTRACT FROM AUTHOR]

Mutations in the MYO7A gene lead to Usher syndrome type 1B (USH1B), a disease characterized by congenital deafness, vision loss, and balance impairment. To create a nonhuman primate (NHP) USH1B model, CRISPR/Cas9 was used to disrupt MYO7A in rhesus macaque zygotes. The targeting efficiency of Cas9 mRNA and hybridized crRNA-tracrRNA (hyb-gRNA) was compared to Cas9 nuclease (Nuc) protein and synthetic single guide (sg)RNAs. Nuc/sgRNA injection led to higher editing efficiencies relative to mRNA/hyb-gRNAs. Mutations were assessed by preimplantation genetic testing (PGT) and those with the desired mutations were transferred into surrogates. A pregnancy was established from an embryo where 92.1% of the PGT sequencing reads possessed a single G insertion that leads to a premature stop codon. Analysis of single peripheral blood leukocytes from the infant revealed that half the cells possessed the homozygous single base insertion and the remaining cells had the wild-type MYO7A sequence. The infant showed sensitive auditory thresholds beginning at 3 months. Although further optimization is needed, our studies demonstrate that it is feasible to use CRISPR technologies for creating NHP models of human diseases. [ABSTRACT FROM AUTHOR]

Objective: Prevention of eating disorders (EDs) is of high importance. However, digital programs with human moderation are unlikely to be disseminated widely. The aim of this study was to test whether a chatbot (i.e., computer program simulating human conversation) would significantly reduce ED risk factors (i.e., weight/shape concerns, thin‐ideal internalization) in women at high risk for an ED, compared to waitlist control, as well as whether it would significantly reduce overall ED psychopathology, depression, and anxiety and prevent ED onset. Method: Women who screened as high risk for an ED were randomized (N = 700) to (1) chatbot based on the StudentBodies© program; or (2) waitlist control. Participants were followed for 6 months. Results: For weight/shape concerns, there was a significantly greater reduction in intervention versus control at 3‐ (d = −0.20; p =.03) and 6‐m‐follow‐up (d = −0.19; p =.04). There were no differences in change in thin‐ideal internalization. The intervention was associated with significantly greater reductions than control in overall ED psychopathology at 3‐ (d = −0.29; p =.003) but not 6‐month follow‐up. There were no differences in change in depression or anxiety. The odds of remaining nonclinical for EDs were significantly higher in intervention versus control at both 3‐ (OR = 2.37, 95% CI [1.37, 4.11]) and 6‐month follow‐ups (OR = 2.13, 95% CI [1.26, 3.59]). Discussion: Findings provide support for the use of a chatbot‐based EDs prevention program in reducing weight/shape concerns through 6‐month follow‐up, as well as in reducing overall ED psychopathology, at least in the shorter‐term. Results also suggest the intervention may reduce ED onset. Public Significance: We found that a chatbot, or a computer program simulating human conversation, based on an established, cognitive‐behavioral therapy‐based eating disorders prevention program, was successful in reducing women's concerns about weight and shape through 6‐month follow‐up and that it may actually reduce eating disorder onset. These findings are important because this intervention, which uses a rather simple text‐based approach, can easily be disseminated in order to prevent these deadly illnesses. Trial registration: OSF Registries; https://osf.io/7zmbv [ABSTRACT FROM AUTHOR]

Assume \mathsf {ZF} + \mathsf {AD} + \mathsf {DC}_\mathbb {R}. There is no injection of {}^{<\omega _{1}}{\omega _{1}} (the set of countable length sequences of countable ordinals) into {}^\omega \mathrm {ON} (the class of \omega length sequences of ordinals). There is no injection of [{\omega _{1}}]^{{\omega _{1}}} (the powerset of {\omega _{1}}) into {}^{<{\omega _{1}}}\mathrm {ON} (the class of countable length sequences of ordinals). [ABSTRACT FROM AUTHOR]

In \mathsf {ZFC}, if there is a measurable cardinal with infinitely many Woodin cardinals below it, then for every binary relation R \in L(\mathbb {R}) on \mathbb {R} with all sections {\mathbf {\Delta }_{1}^{1}} ({\mathbf {\Sigma }_{1}^{1}} or {\mathbf {\Pi }_{1}^{1}}) and every \sigma-ideal I on \mathbb {R} so that the associated forcing \mathbb {P}_I of I^+ {\mathbf {\Delta }_{1}^{1}} subsets is proper, there exists some I^+ {\mathbf {\Delta }_{1}^{1}} set C so that R \cap (C \times \mathbb {R}) is {\mathbf {\Delta }_{1}^{1}} ({\mathbf {\Sigma }_{1}^{1}} or {\mathbf {\Pi }_{1}^{1}}, respectively). [ABSTRACT FROM AUTHOR]

CD8 T cells play a key role in cancer immunotherapy and allograft rejection. However, it is not clear how they kill cells and tissues that do not have the agonist peptide-major histocompatibility complex (MHC) on their surface, as in the settings of MHC class I deficient tumors and indirect rejection of MHC-mismatched transplants. CD8 T cells might respond to agonist antigen cross-presented on hematopoietic cells, leading to a "bystander" rejection. Alternatively, they may recognize agonist antigen cross-presented on recipient endothelial cells and kill the tissue's vital blood supply. The latter mechanism predicts that all non-vascularized grafts, grafts dependent on in-growth of recipient blood vessels, will be susceptible to CD8 T cell mediated indirect rejection. In contrast, we show here that non-vascularized transplants, bearing the same agonist antigen, are not universally susceptible to this rejection pathway. Non-vascularized skin, but not islet or heart tissue transplants were indirectly rejected by CD8 T cells. Furthermore, CD8 T cells were able to indirectly reject skin grafts when recipient MHC class I expression was restricted to bone marrow derived cells but not when it was restricted to radioresistant cells (e.g. endothelial cells). These findings argue against a major role for endothelial cell cross-presentation in killing of tissue that does not present the agonist peptide-MHC class I. Instead, the data suggests that cross-presentation by recipient hematopoietic cells underlies the CD8 T cell mediated killing of tissue that is unable to directly present the target peptide-MHC class I. [ABSTRACT FROM AUTHOR]

Background: Chatbots have the potential to provide cost-effective mental health prevention programs at scale and increase interactivity, ease of use, and accessibility of intervention programs. Objective: The development of chatbot prevention for eating disorders (EDs) is still in its infancy. Our aim is to present examples of and solutions to challenges in designing and refining a rule-based prevention chatbot program for EDs, targeted at adult women at risk for developing an ED. Methods: Participants were 2409 individuals who at least began to use an EDs prevention chatbot in response to social media advertising. Over 6 months, the research team reviewed up to 52,129 comments from these users to identify inappropriate responses that negatively impacted users' experience and technical glitches. Problems identified by reviewers were then presented to the entire research team, who then generated possible solutions and implemented new responses. Results: The most common problem with the chatbot was a general limitation in understanding and responding appropriately to unanticipated user responses. We developed several workarounds to limit these problems while retaining some interactivity. Conclusions: Rule-based chatbots have the potential to reach large populations at low cost but are limited in understanding and responding appropriately to unanticipated user responses. They can be most effective in providing information and simple conversations. Workarounds can reduce conversation errors. [ABSTRACT FROM AUTHOR]

Humans are extraordinarily social, and social isolation has profound effects on our behavior, ranging from increased social motivation following short periods of social isolation to increased anti-social behaviors following long-term social isolation. Mice are frequently used as a model to understand how social isolation impacts the brain and behavior. While the effects of chronic social isolation on mouse social behavior have been well studied, much less is known about how acute isolation impacts mouse social behavior and whether these effects vary according to the sex of the mouse and the behavioral context of the social encounter. To address these questions, we characterized the effects of acute (3-day) social isolation on the vocal and non-vocal social behaviors of male and female mice during same-sex and opposite-sex social interactions. Our experiments uncovered pronounced effects of acute isolation on social interactions between female mice, while revealing more subtle effects on the social behaviors of male mice during same-sex and opposite-sex interactions. Our findings advance the study of same-sex interactions between female mice as an attractive paradigm to investigate neural mechanisms through which acute isolation enhances social motivation and promotes social behavior. [ABSTRACT FROM AUTHOR]

With rising complexity of percutaneous coronary interventions being performed, the incidence of cardiac arrest in the cardiac catheterization laboratory (CCL) is likely to increase. The authors undertook a series of multidisciplinary simulation sessions to identify practice deficiencies and propose solutions to improve patient care. Five simulation sessions were held at Western Health CCL to simulate different cardiac arrest scenarios. Participants included cardiologists, intensivists, anesthetists, nurses, and technicians. Post-simulation feedback was analyzed qualitatively. Challenges encountered were grouped into 4 areas: (1) communication and teamwork, (2) equipment, (3) vascular access and drugs, and (4) physical environment and radiation exposure. Proposed solutions included regular simulation training; increasing familiarity with the physical environment, utilization of specialized equipment; and formation of 2 team leaders to improve efficiency. Cardiac arrest in the CCL is a unique clinical event that necessitates specific training to improve technical and nontechnical skills with potential to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

If 𝒩 is a proper Polish metric space and ℳ is any countable dense submetric space of 𝒩 , then the Scott rank of 𝒩 in the natural first-order language of metric spaces is countable and in fact at most ω 1 ℳ + 1 , where ω 1 ℳ is the Church–Kleene ordinal of ℳ (construed as a subset of ω) which is the least ordinal with no presentation on ω computable from ℳ. If 𝒩 is a rigid Polish metric space and ℳ is any countable dense submetric space, then the Scott rank of 𝒩 is countable and in fact less than ω 1 ℳ . [ABSTRACT FROM AUTHOR]

Background Modern permanent pacemakers (PPMs) have individual features designed to identify cardiac rhythm abnormalities and improve their performance. Inappropriate pacing inhibition may be an undesired outcome from these features and cause symptoms in patients who require frequent pacing, leading to dizziness, and syncope. Inappropriate inhibition can be difficult to identify in circumstances that are intermittent and difficult to reproduce. Case summary A 57-year-old female underwent a mitral valve replacement (MVR) for severe mitral stenosis. One month following MVR, she presented with symptomatic third-degree atrioventricular block, and a dual-chamber PPM (Advisa™, Medtronic, Minneapolis, USA) was implanted and programmed DDD 50–130 b.p.m. At the 3-month follow-up, she reported frequent episodes of lightheadedness. She was found to have intermittent ventricular pacing inhibition on a 48-h Holter monitor due to an internal function of the Advisa™ series of PPMs that attempts to store an electrogram (EGM) every 1 h and 30 s. During the EGM storage, an amplified signal from the storage capacitor can result in oversensing by the ventricular channel and inappropriate pacing inhibition. Discussion To rectify the issue, the ventricular lead sensitivity value was increased from 0.9 mV to 1.2 mV. No instances of inappropriate ventricular pacing inhibition were noted on follow-up. To our knowledge, this is a rare case of inappropriate ventricular pacing inhibition caused by a combination of PPM self-adjusting sensitivity algorithm and oversensing every 1 h and 30 s from an amplified storage capacitor. Physicians should be aware of this possible complication and differentiate it from device or lead malfunction. [ABSTRACT FROM AUTHOR]

We work throughout in the theory \mathsf {ZF} with the axiom of determinacy, \mathsf {AD}. We introduce and prove some club uniformization principles under \mathsf {AD} and \mathsf {AD}_\mathbb{R}. Using these principles, we establish continuity results for functions of the form \Phi \colon [{\omega _{1}}]^{\omega _{1}} \rightarrow {\omega _{1}} and \Psi \colon [{\omega _{1}}]^{\omega _{1}} \rightarrow {}^{\omega _{1}}{\omega _{1}}. Specifically, for every function \Phi \colon [\omega _1]^{\omega _1} \rightarrow \omega _1, there is a club C \subseteq \omega _1 so that \Phi \upharpoonright [C]^{\omega _1}_* is a continuous function. This has several consequences such as establishing the cardinal relation \vert[{\omega _{1}}]^{<{\omega _{1}}}\vert < \vert[{\omega _{1}}]^{\omega _{1}}\vert and answering a question of Zapletal by showing that if \langle X_\alpha : \alpha < \omega _1\rangle is a collection of subsets of [\omega _1]^{\omega _1} with the property that \bigcup _{\alpha < \omega _1}X_\alpha = [\omega _1]^{\omega _1}, then there is an \alpha < \omega _1 so that X_\alpha and [\omega _1]^{\omega _1} are in bijection. We show that under \mathsf {AD}_\mathbb{R} everywhere [\omega _1]^{<\omega _1}-club uniformization holds which is the following statement: Let \mathsf {club}_{\omega _1} denote the collection of club subsets of \omega _1. Suppose R \subseteq [\omega _1]^{<\omega _1} \times \mathsf {club}_{\omega _1} is \subseteq -downward closed in the sense that for all \sigma \in [\omega _1]^{<\omega _1}, for all clubs C \subseteq D, R(\sigma,D) implies R(\sigma,C). Then there is a function F \colon {\mathrm {dom}}(R) \rightarrow \mathsf {club}_{\omega _1} so that for all \sigma \in {\mathrm {dom}}(R), R(\sigma,F(\sigma)). We show that under \mathsf {AD} almost everywhere [{\omega _{1}}]^{<{\omega _{1}}}-club uniformization holds which is the statement that for every R \subseteq [{\omega _{1}}]^{<{\omega _{1}}} \times \mathsf {club}_{\omega _{1}} which is \subseteq -downward closed, there is a club C and a function F \colon {\mathrm {dom}}(R) \cap [C]^{<{\omega _{1}}}_* \rightarrow \mathrm {club}_{\omega _{1}} so that for all \sigma \in {\mathrm {dom}}(R) \cap [C]^{<{\omega _{1}}}_*, R(\sigma,F(\sigma)). [ABSTRACT FROM AUTHOR]

ZF + AD proves that for all nontrivial forcings ℙ on a wellorderable set of cardinality less than Θ, 1 ℙ ⊨ ℙ ¬ AD . ZF + AD + Θ is regular proves that for all nontrivial forcing ℙ which is a surjective image of ℝ, 1 ℙ ⊨ ℙ ¬ AD . In particular, ZF + AD + V = L(ℝ) proves that for every nontrivial forcing ℙ ∈ L Θ (ℝ) , 1 ℙ ⊨ ℙ ¬ AD . [ABSTRACT FROM AUTHOR]

Purpose: Accurate and timely diagnosis of breast carcinoma is very crucial because of its high incidence and high morbidity. Screening can improve overall prognosis by detecting the disease early. Biopsy remains as the gold standard for pathological confirmation of malignancy and tumour grading. The development of diagnostic imaging techniques as an alternative for the rapid and accurate characterization of breast masses is necessitated. Quantitative ultrasound (QUS) spectroscopy is a modality well suited for this purpose. This study was carried out to evaluate different texture analysis methods applied on QUS spectral parametric images for the characterization of breast lesions. Methods: Parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined using QUS spectroscopy from 193 patients with breast lesions. Texture methods were used to quantify heterogeneities of the parametric images. Three statistical-based approaches for texture analysis that include Gray Level Co-occurrence Matrix (GLCM), Gray Level Run-length Matrix (GRLM), and Gray Level Size Zone Matrix (GLSZM) methods were evaluated. QUS and texture-parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis in order to classify breast lesions as either benign or malignant. We developed a diagnostic model using different classification algorithms including linear discriminant analysis (LDA), k-nearest neighbours (KNN), support vector machine with radial basis function kernel (SVM-RBF), and an artificial neural network (ANN). Model performance was evaluated using leave-one-out cross-validation (LOOCV) and hold-out validation. Results: Classifier performances ranged from 73% to 91% in terms of accuracy dependent on tumour margin inclusion and classifier methodology. Utilizing information from tumour core alone, the ANN achieved the best classification performance of 93% sensitivity, 88% specificity, 91% accuracy, 0.95 AUC using QUS parameters and their GLSZM texture features. Conclusions: A QUS-based framework and texture analysis methods enabled classification of breast lesions with >90% accuracy. The results suggest that optimizing method for extracting discriminative textural features from QUS spectral parametric images can improve classification performance. Evaluation of the proposed technique on a larger cohort of patients with proper validation technique demonstrated the robustness and generalization of the approach. [ABSTRACT FROM AUTHOR]

Introduction: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo‐atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs. Methods: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA–VA) was also measured. Results: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p <.001). The StimA–VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p <.001). The ∆VA and StimA–VA were always ≤40 ms in patients with non‐decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left. Conclusion: ΔVA and StimA–VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation. [ABSTRACT FROM AUTHOR]

Background: Stroke rates and risk factors may change as percutaneous coronary intervention practice evolves and no data are available comparing stroke incidence after percutaneous coronary intervention to the general population. Aims: This study aimed to identify the incidence and risk factors for inpatient and subsequent stroke following percutaneous coronary intervention with comparison to age-matched controls. Methods: Data were prospectively collected from 22,618 patients undergoing percutaneous coronary intervention in the Melbourne Interventional Group registry (2005–2015). The cohort was compared to the North-East Melbourne Stroke Incidence Study population-based cohort (1997–1999) and predefined variables assessed for association with inpatient or outpatient stroke. Results: Inpatient stroke occurred in 0.33% (65.3% ischemic, 28.0% haemorrhagic, and 6.7% cause unknown), while outpatient stroke occurred in 0.55%. Inpatient and outpatient stroke were associated with higher rates of in-hospital major adverse cardiovascular outcomes (p < 0.0001) and mortality (p < 0.0001), as well as 12-month mortality (p < 0.0001). Factors independently associated with inpatient stroke were renal impairment, ST-elevation myocardial infarction, previous stroke, left ventricular ejection fraction 30–45%, and female sex, while those associated with outpatient stroke were previous stroke, chronic lung disease, previous myocardial infarction, rheumatoid arthritis, female sex, and older age. Compared to the age-standardized population-based cohort, stroke rates in the 12 months following discharge were higher for percutaneous coronary intervention patients <65 years old, but lower for percutaneous coronary intervention patients ≥65 years old. Conclusions: Risk of inpatient stroke following percutaneous coronary intervention appears to be largely associated with clinical status at presentation, while outpatient stroke relates more to age and chronic disease. Compared to the general population, outpatient stroke rates following percutaneous coronary intervention are higher for younger, but not older, patients. [ABSTRACT FROM AUTHOR]