Miracle-dz/UniFAR-FTUs huggingface dataset:
Replicating autobiographical memory research using social media: a case study

ABSTRACT The durability of memories for personally experienced events and the effectiveness of naturalistically generated cues of those events were investigated via a case study using Timehop to re-present information from Facebook, Twitter, and the iPhone photograph archive from the past six years to generate autobiographical memories. Replicating prior longitudinal self-studies of remembering, recency predicted successful recall of specific events. Prior research showing images to be more evocative of autobiographical remembering than text was also replicated here. Results also supported claims that direct retrieval is a common mode of remembering. Somewhat surprisingly, retrieval of autobiographical memories had little influence on ongoing affect, cognition, and behaviour. This is suggested as “proof of concept” that social media data allows for modern replication of diary-type studies and expansion beyond typical participant pools. The interrelated functions of social media for remembering and of autobiographical remembering to social media can also be explored with this method.
National Early Warning Score 2 (NEWS2) to identify inpatient COVID-19 deterioration: a retrospective analysis.

INTRODUCTION We sought to provide the first report of the use of NEWS2 monitoring to pre-emptively identify clinical deterioration within hospitalised COVID-19 patients. METHODS Consecutive adult admissions with PCR-confirmed COVID-19 were included in this single-centre retrospective UK cohort study. We analysed all electronic clinical observations recorded within 28 days of admission until discharge or occurrence of a serious event, defined as any of the following: initiation of respiratory support, admission to intensive care, initiation of end of life care, or in-hospital death. RESULTS 133/296 (44.9%) patients experienced at least one serious event. NEWS2 ≥ 5 heralded the first occurrence of a serious event with sensitivity 0.98 (95% CI 0.96-1.00), specificity 0.28 (0.21-0.35), positive predictive value (PPV) 0.53 (0.47-0.59), and negative predictive value (NPV) 0.96 (0.90-1.00). The NPV (but not PPV) of NEWS2 monitoring exceeded that of other early warning scores including the Modified Early Warning Score (MEWS) (0.59 [0.52-0.66], p<0.001) and quick Sepsis Related Organ Failure Assessment (qSOFA) score (0.58 [0.51-0.65], p<0.001). CONCLUSION Our results support the use of NEWS2 monitoring as a sensitive method to identify deterioration of hospitalised COVID-19 patients, albeit at the expense of a relatively high false-trigger rate.
Effectiveness of Pain Neurophysiology Education on Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES To estimate the effectiveness and safety of Pain Neurophysiology Education (PNE) on pain, disability, and psychological distress at post-intervention and long-term (closest to twelve months after initiating the intervention) in musculoskeletal pain (MSKP). METHODS Randomized Controlled Trials (RCT) were identified in six engines, reference lists, ClinicalTrials.gov, and by contacting key researches. Risk of bias was assessed using Cochrane Collaboration Risk of Bias Tool 2.0. Meta-analyses, using Restricted Maximum Likelihood Method, were conducted to estimate standardized mean differences (SMD) and overall quality of evidence was evaluated according to GRADE. RESULTS In total, 18 RCTs (n = 1,585) were included. There was small to moderate effects of PNE on pain at post-intervention and long-term: SMD = -0.32 (95% confidence interval [CI]: -.58; -.05) and SMD = -0.40 (95% CI: -.78; -.03), respectively. On disability, PNE had a small effect at post-intervention: SMD = -0.17 (95% CI: -.34; -.01) but was insignificant at long-term: SMD = -0.27 (95% CI: -.59; .06). Likewise, there was a small to moderate effect on psychological distress at post-intervention: SMD = -0.36 (95% CI: -.67; -.06) but was insignificant at long-term: SMD = -0.37 (95% CI: -.75; .01). Quality of evidence was low across all outcomes. Additional analyses showed significant effects of PNE, corresponding to moderate effects, on pain and psychological distress at both time points in chronic MSKP. CONCLUSIONS Overall quality of evidence was low, supporting PNE being safe and having small to moderate effects on pain at both time points, and on disability as well as psychological distress at post-intervention.
Hospital-based acute care in the last 30 days of life among patients with chronic disease that received early, late or no specialist palliative care: a retrospective cohort study of eight chronic disease groups

Objective For eight chronic diseases, evaluate the association of specialist palliative care (PC) exposure and timing with hospital-based acute care in the last 30 days of life. Design Retrospective cohort study using administrative data. Setting Alberta, Canada between 2007 and 2016. Participants 47 169 adults deceased from: (1) cancer, (2) heart disease, (3) dementia, (4) stroke, (5) chronic lower respiratory disease (chronic obstructive pulmonary disease (COPD)), (6) liver disease, (7) neurodegenerative disease and (8) renovascular disease. Main outcome measures The proportion of decedents who experienced high hospital-based acute care in the last 30 days of life, indicated by ≥two emergency department (ED) visit, ≥two hospital admissions,≥14 days of hospitalisation, any intensive care unit (ICU) admission, or death in hospital. Relative risk (RR) and risk difference (RD) of hospital-based acute care given early specialist PC exposure (≥90 days before death), adjusted for patient characteristics. Results In an analysis of all decedents, early specialist PC exposure was associated with a 32% reduction in risk of any hospital-based acute care as compared with those with no PC exposure (RR 0.69, 95% CI 0.66 to 0.71; RD 0.16, 95% CI 0.15 to 0.17). The association was strongest in cancer-specific analyses (RR 0.53, 95% CI 0.50 to 0.55; RD 0.31, 95% CI 0.29 to 0.33) and renal disease-specific analyses (RR 0.60, 95% CI 0.43 to 0.84; RD 0.22, 95% CI 0.11 to 0.34), but a~25% risk reduction was observed for each of heart disease, COPD, neurodegenerative diseases and stroke. Early specialist PC exposure was associated with reducing risk of four out of five individual indicators of high hospital-based acute care in the last 30 days of life, including ≥two ED visit,≥two hospital admission, any ICU admission and death in hospital. Conclusions Early specialist PC exposure reduced the risk of hospital-based acute care in the last 30 days of life for all chronic disease groups except dementia.
Smoking prevalence, core/periphery network positions, and peer influence: Findings from five datasets on US adolescents and young adults

Smoking prevalence has decreased significantly among US adolescents and young adults in the past 20 years. It is possible that adolescent and young adult smokers were moving from core to peripheral positions in social networks and thus less influential as suggested in previous research on adult smokers. We construct five sample datasets to test these hypotheses but none of them receives much support. When the proportion of smokers is relatively higher in two sample datasets, smokers tended to be at more marginal network positions than nonsmokers, both smokers and nonsmoker could exert peer influence, and the magnitude of peer influence from smokers was even greater than that from nonsmokers. When smoking was less frequent in the other three sample datasets, smokers and nonsmokers were at random network positions and no peer influence on smoking behavior was detected. Therefore, core/periphery network positions are still the key linking smoking prevalence and peer influence among US adolescents and young adults but operating through a different mechanism from their adult counterparts. When scientists design and conduct prevention programs against adolescent and young adult smoking behavior, core/periphery network positions, smoking prevalence, and peer influence should all be taken into consideration.
Resilience in the face of pelvic pain: A pilot study in males and females affected by urologic chronic pelvic pain

Resilience represents a fundamental element in the experience of pain, as it allows adaptation to suffering and increases psychological social well‐being and quality of life (QoL). We investigated resilience in patients affected by urologic chronic pelvic pain (UCPP) and the relationships with pain severity and distribution, catastrophizing and psychological distress.
Smartphone usage among people living with severe visual impairment and blindness

ABSTRACT Low vision care and rehabilitation is often limited by access to assistive devices, especially in low-resourced countries, due to their high cost and unavailability. Smartphones have the potential to serve as an alternative assistive device for people living with severe visual impairment and blindness (SVIB). This study aims to investigate the use of smartphones among people living with SVIB. The study was a cross-sectional study of 166 people living with SVIB in a low resourced setting. The participants were recruited from two tertiary institutions and four eye care facilities. A questionnaire was administered to all respondents and for those who could not read prints they were read out to them and their responses recorded. The majority of respondents (n = 88, 53.1%) either had no phone or used a basic phone. The prevalence of smartphone usage among people living with SVIB was found to be 46.90% (n = 78). Most respondents use their smartphones to interact on social media [n = 75 (96%)] and web browsing [n = 69,92%]. The most frequently demanded [n = 22 (44%)] smartphone functionality by the respondents was the image and color description feature. Most participants were unaware that 90% of their functionality demands already existed and were compatible with current smartphones. A significant number of people living with SVIB in this study used smartphones; however, most users are unaware of its full functionality and assistive capabilities.
Effect of basal forebrain somatostatin and parvalbumin neurons in propofol and isoflurane anesthesia

The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma‐aminobutyric acid (GABA) neurons, including somatostatin‐expressing (GABASOM) and parvalbumin‐positive (GABAParv) neurons, function differently in mediating the natural sleep–wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep–wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.
Functional analysis of large MAF transcription factors and elucidation of their relationships with human diseases

The large MAF transcription factor group is a group of transcription factors with an acidic region, a basic region, and a leucine zipper region. Four types of MAF, MAFA, MAFB, c-MAF, and NRL, have been identified in humans and mice. In order to elucidate the functions of the large MAF transcription factor group in vivo, our research group created genetically modified MAFA-, MAFB-, and c-MAF-deficient mice and analyzed their phenotypes. MAFA is expressed in pancreatic β cells and is essential for insulin transcription and secretion. MAFB is essential for the development of pancreatic endocrine cells, formation of inner ears, podocyte function in the kidneys, and functional differentiation of macrophages. c-MAF is essential for lens formation and osteoblast differentiation. Furthermore, a single-base mutation in genes encoding the large MAF transcription factor group causes congenital renal disease, eye disease, bone disease, diabetes, and tumors in humans. This review describes the functions of large MAF transcription factors in vivo and their relationships with human diseases.
Detection of SARS‐CoV‐2‐specific memory B cells to delineate long‐term COVID‐19 immunity

Background: The ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, represents a serious worldwide health concern. A deeper understanding of the immune response to SARS-CoV-2 will be required to refine vaccine development and efficacy as well as to evaluate long-term immunity in convalescent patients. With this in mind, we investigated the formation of SARS-CoV-2 specific BMEMORY cells from patient blood samples. Methods: A standard flow cytometry-based protocol for the detection of SARS-CoV-2 specific B cells was applied using fluorochrome-coupled SARS-CoV-2 spike (S) full-length protein. Cohorts of 26 central European convalescent mild/moderate COVID-19 patients and 14 healthy donors were assessed for the levels of SARS-CoV-2 S- specific BMEMORY cells. Results: Overall B cell composition was not affected by SARS-CoV-2 infection in convalescent patients. Our analysis of SARS-CoV-2 specific BMEMORY cells in samples collected at different time points revealed that S-protein specific B cells remain in peripheral blood at least up to 6 months after COVID-19 diagnosis. Conclusions: Detection of SARS-CoV-2 specific BMEMORY cells may improve our understanding of the long-term adaptive immunity in response to SARS-CoV-2, allowing for an improved public health response and vaccine development during the COVID-19 pandemic. Further validation of the study in larger and more diverse populations and a more extended observation period will be required.
MAGI-1 PDZ2 Domain Blockade Averts Adenovirus Infection via Enhanced Proteolysis of the Apical Coxsackievirus and Adenovirus Receptor

Adenovirus is a common threat in immunosuppressed populations and military recruits. There are no currently approved treatments/prophylactic agents that protect from most AdV infections. ABSTRACT Adenoviruses (AdVs) are etiological agents of gastrointestinal, heart, eye, and respiratory tract infections that can be lethal for immunosuppressed people. Many AdVs use the coxsackievirus and adenovirus receptor (CAR) as a primary receptor. The CAR isoform resulting from alternative splicing that includes the eighth exon, CAREx8, localizes to the apical surface of polarized epithelial cells and is responsible for the initiation of AdV infection. We have shown that the membrane level of CAREx8 is tightly regulated by two MAGI-1 PDZ domains, PDZ2 and PDZ4, resulting in increased or decreased AdV transduction, respectively. We hypothesized that targeting the interactions between the MAGI-1 PDZ2 domain and CAREx8 would decrease the apical CAREx8 expression level and prevent AdV infection. Decoy peptides that target MAGI-1 PDZ2 were synthesized (TAT-E6 and TAT-NET1). PDZ2 binding peptides decreased CAREx8 expression and reduced AdV transduction. CAREx8 degradation was triggered by the activation of the regulated intramembrane proteolysis (RIP) pathway through a disintegrin and metalloproteinase (ADAM17) and γ-secretase. Further analysis revealed that ADAM17 interacts directly with the MAGI-1 PDZ3 domain, and blocking the PDZ2 domain enhanced the accessibility of ADAM17 to the substrate (CAREx8). Finally, we validated the efficacy of TAT-PDZ2 peptides in protecting the epithelia from AdV transduction in vivo using a novel transgenic animal model. Our data suggest that TAT-PDZ2 binding peptides are novel anti-AdV molecules that act by enhanced RIP of CAREx8 and decreased AdV entry. This strategy has additional translational potential for targeting other viral receptors that have PDZ binding domains, such as the angiotensin-converting enzyme 2 receptor. IMPORTANCE Adenovirus is a common threat in immunosuppressed populations and military recruits. There are no currently approved treatments/prophylactic agents that protect from most AdV infections. Here, we developed peptide-based small molecules that can suppress AdV infection of polarized epithelia by targeting the AdV receptor, coxsackievirus and adenovirus receptor (CAREx8). The newly discovered peptides target a specific PDZ domain of the CAREx8-interacting protein MAGI-1 and decrease AdV transduction in multiple polarized epithelial models. Peptide-induced CAREx8 degradation is triggered by extracellular domain (ECD) shedding through ADAM17 followed by γ-secretase-mediated nuclear translocation of the C-terminal domain. The enhanced shedding of the CAREx8 ECD further protected the epithelium from AdV infection. Taken together, these novel molecules protect the epithelium from AdV infection. This approach may be applicable to the development of novel antiviral molecules against other viruses that use a receptor with a PDZ binding domain.
Fitness costs of individual and combined pyrethroid resistance mechanisms, kdr and CYP-mediated detoxification, in Aedes aegypti

Background Aedes aegypti is an important vector of many human diseases and a serious threat to human health due to its wide geographic distribution and preference for human hosts. A. aegypti also has evolved widespread resistance to pyrethroids due to the extensive use of this insecticide class over the past decades. Mutations that cause insecticide resistance result in fitness costs in the absence of insecticides. The fitness costs of pyrethroid resistance mutations in A. aegypti are still poorly understood despite their implications for arbovirus transmission. Methodology/Principle findings We evaluated fitness based both on allele-competition and by measuring specific fitness components (i.e. life table and mating competition) to determine the costs of the different resistance mechanisms individually and in combination. We used four congenic A. aegypti strains: Rockefeller (ROCK) is susceptible to insecticides; KDR:ROCK (KR) contains only voltage-sensitive sodium channel (Vssc) mutations S989P+V1016G (kdr); CYP:ROCK (CR) contains only CYP-mediated resistance; and CYP+KDR:ROCK (CKR) contains both CYP-mediated resistance and kdr. The kdr allele frequency decreased over nine generations in the allele-competition study regardless of the presence of CYP-mediated resistance. Specific fitness costs were variable by strain and component measured. CR and CKR had a lower net reproductive rate (R0) than ROCK or KR, and KR was not different than ROCK. There was no correlation between the level of permethrin resistance conferred by the different mechanisms and their fitness cost ratio. We also found that CKR males had a reduced mating success relative to ROCK males when attempting to mate with ROCK females. Conclusions/Significance Both kdr and CYP-mediated resistance have a fitness cost affecting different physiological aspects of the mosquito. CYP-mediated resistance negatively affected adult longevity and mating competition, whereas the specific fitness costs of kdr remains elusive. Understanding fitness costs helps us determine whether and how quickly resistance will be lost after pesticide application has ceased.
Evaluating the biomechanical characteristics of cuffed-tracheostomy tubes using finite element analysis

Abstract The objective of this study was to perform finite element analysis (FEA) of cuff inflation within an anatomically accurate model of an adult trachea in four different cuffed-tracheostomy tube designs. The leakage quantified by the distance between the cuff and trachea was largest for the Tracoe cuff and smallest for the Portex cuff. The smooth muscle stresses were greatest for the Portex and least for the Distal cuff, respectively. The proposed FEA model offers a promising approach to virtually evaluate the sealing efficacy of cuffed-tracheostomy tubes and the tracheal wall stresses induced by cuff inflation, prior to application.
Factors associated with ordering food via online meal ordering services

Abstract Objective: Online meal ordering services are increasing in popularity in Australia and globally. Meals ordered online for home delivery are typically less healthy than home-made meals, potentially contributing to weight gain. The aim of the present study was to identify the types of consumers who are most likely to engage in online meal ordering. Design: A cross-sectional survey including items relating to demographic and lifestyle factors was disseminated via a web panel provider. Setting: Australia. Participants: A total of 2010 Australian adults aged 18+ years. Results: More than a quarter of respondents (28 %) engaged in online meal ordering at least once in the previous month. Younger respondents, those with a higher BMI, and those with higher education and income levels were more likely to have done so. Consuming higher levels of sugary drinks and fast-food restaurant patronage were significantly associated with ordering meals online for home delivery. Conclusions: The outcomes of this study suggest that the use of online meal ordering services is becoming a common practice in Australia, and it is therefore important to implement evidence-based strategies and policies to encourage individuals to make healthy food choices when using these services.
Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma

Significance High-risk neuroblastoma accounts for nearly 15% of all pediatric cancer-related deaths. MYCN is an oncogene amplified in roughly half of high-risk neuroblastoma cases and finding new therapies to neutralize MYCN is a high priority for pediatric cancer. Here we demonstrate that MYCN-amplified neuroblastomas are sensitive to the combined inhibition of MCT1 and complex I of the mitochondrion. Sensitivity is due to low expression of MCT4 and high expression of MCT1 and the MCT1 chaperone CD147. Pharmacologic inhibition with AZD3965 and phenformin leads to complementary inhibition of metabolic processes that ultimately leads to cell death. MYCN-amplified neuroblastoma is a lethal subset of pediatric cancer. MYCN drives numerous effects in the cell, including metabolic changes that are critical for oncogenesis. The understanding that both compensatory pathways and intrinsic redundancy in cell systems exists implies that the use of combination therapies for effective and durable responses is necessary. Additionally, the most effective targeted therapies exploit an “Achilles’ heel” and are tailored to the genetics of the cancer under study. We performed an unbiased screen on select metabolic targeted therapy combinations and correlated sensitivity with over 20 subsets of cancer. We found that MYCN-amplified neuroblastoma is hypersensitive to the combination of an inhibitor of the lactate transporter MCT1, AZD3965, and complex I of the mitochondrion, phenformin. Our data demonstrate that MCT4 is highly correlated with resistance to the combination in the screen and lowly expressed in MYCN-amplified neuroblastoma. Low MCT4 combines with high expression of the MCT2 and MCT1 chaperone CD147 in MYCN-amplified neuroblastoma, altogether conferring sensitivity to the AZD3965 and phenformin combination. The result is simultaneous disruption of glycolysis and oxidative phosphorylation, resulting in dramatic disruption of adenosine triphosphate (ATP) production, endoplasmic reticulum stress, and cell death. In mouse models of MYCN-amplified neuroblastoma, the combination was tolerable at concentrations where it shrank tumors and did not increase white-blood-cell toxicity compared to single drugs. Therefore, we demonstrate that a metabolic combination screen can identify vulnerabilities in subsets of cancer and put forth a metabolic combination therapy tailored for MYCN-amplified neuroblastoma that demonstrates efficacy and tolerability in vivo.