Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term trends in critical care admissions in Wales *

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18–64 years), older (65–79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered ‘fit’ rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.
Factors associated with behavioral intention of free and self-paid severe acute respiratory coronavirus virus 2 (SARS-CoV-2) vaccination based on the social cognitive theory among nurses and doctors in China

Abstract Objective: To examine the associations between factors based on the social cognitive theory (SCT) and behavioral intention among doctors and nurses in China toward free and self-paid (600 RMB or US$91) severe acute respiratory coronavirus virus 2 (SARS-CoV-2) vaccination given 80% effectiveness and rare mild side effects. Design: Cross-sectional study. Setting: Public hospitals. Participants: The study included 362 doctors and 1,702 nurses in major departments of 5 hospitals of 3 Chinese provinces. Methods: An anonymous online survey was conducted from October to November 2020, facilitated by hospital administrators through online WeChat/QQ working groups. Data on outcome expectations, self-efficacy, norms, and COVID-19–related work experiences were collected. Multivariate logistic regression models were used for data analyses. Results: The logistic regression analysis showed that physical (eg, protective effect of vaccination) and self-evaluative outcome expectations (eg, anticipated regret), self-efficacy, norms (eg, descriptive norm, subjective norm, professional norm, and moral norm), and job satisfaction were significantly and positively associated with the free and self-paid SARS-CoV-2 vaccination intention outcomes among doctors and nurses, adjusted for background variables. Doctors who had engaged in COVID-19–related work reported higher self-paid vaccination intention. Conclusions: Health promotion is needed to improve the uptake of SARS-CoV-2 vaccination among healthcare workers. Such interventions may consider modifying the identified factors of vaccination intention, including strengthening perceived efficacy, positive feelings about vaccination, the need to avoid future regret, self-efficacy, and social norms. Future studies should examine the actual behavior patterns of SARS-CoV-2 vaccination, and the efficacy of promotion intervention should be tested in randomized controlled studies.
Revisiting the drivers of acoustic similarities in tropical anuran assemblages.

Acoustic signaling is key in mediating mate-choice, which directly impacts individual fitness. Because background noise and habitat structure can impair signal transmission, the acoustic space of mixed-species assemblages has long been hypothesized to reflect selective pressures against signal interference and degradation. However, other potential drivers that received far less attention can drive similar outputs on the acoustic space. Phylogenetic niche conservatism and allometric constraints may also modulate species acoustic features, and the acoustic space of communities could be a side-effect of ecological assembly processes involving other traits (e.g. environmental filtering). Additionally, the acoustic space can also reflect the sorting of species relying on public information through extended communication networks. Using an integrative approach, we revisit the potential drivers of the acoustic space by addressing the distribution of acoustic traits, body size, and phylogenetic relatedness in tropical anuran assemblages across gradients of environmental heterogeneity in the Pantanal wetlands. We found the overall acoustic space to be aggregated compared with null expectations, even when accounting for confounding effects of body size. Across assemblages, acoustic and phylogenetic differences were positively related, while acoustic and body size similarities were negatively related, although to a minor extent. We suggest that acoustic partitioning, acoustic adaptation, and allometric constraints play a minor role in shaping the acoustic output of tropical anuran assemblages and that phylogenetic niche conservatism and public information use would influence between-assemblage variation. Our findings highlight an overlooked multivariate nature of the acoustic dimension and underscore the importance of including the ecological context of communities to understand drivers of the acoustic space.
Fixed-dose combination amlodipine–celecoxib for treatment of hypertension and osteoarthritis pain: an up-to-date evaluation

ABSTRACT Introduction: A fixed-dose combination of amlodipine and celecoxib, branded in the USA as Consensi®, was recently granted a US Food and Drug Administration (FDA)-approved indication for treatment of comorbid hypertension and osteoarthritis. Areas covered: A PubMed and Medline search was conducted for clinical trials published through December 2020 in the English language using keywords amlodipine, celecoxib, combination product, consensi, hypertension, osteoarthritis, and pill burden. Although no clinical trials have been published in the peer-reviewed literature, results from two phase 3 clinical trials reported to ClinicalTrials.gov suggest that amlodipine–celecoxib has similar short-term efficacy compared with amlodipine alone in reducing blood pressure and a comparable adverse event profile to the individual components administered alone. Expert opinion: Despite the pill burden reduction and a body of evidence supporting the efficacy and safety of the individual drugs, the role of amlodipine–celecoxib in the management of patients with hypertension–osteoarthritis remains in question. This is in no small part because the combination product is very costly relative to the generic components, provides limited flexibility for dose-adjustment, and lacks long-term data on safety and efficacy.
Unusual characteristics of the carbon cycle during the 2015−2016 El Niño

The 2015−2016 El Niño was one of the strongest on record, but its influence on the carbon balance is less clear. Using Northern Hemisphere atmospheric CO2 observations, we found both detrended atmospheric CO2 growth rate (CGR) and CO2 seasonal‐cycle amplitude (SCA) of 2015−2016 were much higher than that of other El Niño events. The simultaneous high CGR and SCA were unusual, because our analysis of long‐term CO2 observations at Mauna Loa revealed a significantly negative correlation between CGR and SCA. Atmospheric inversions and terrestrial ecosystem models indicate strong northern land carbon uptake during spring but substantially reduced carbon uptake (or high emissions) during early autumn, which amplified SCA but also resulted in a small anomaly in annual carbon uptake of northern ecosystems in 2015−2016. This negative ecosystem carbon uptake anomaly in early autumn was primarily due to soil water deficits and more litter decomposition caused by enhanced spring productivity. Our study demonstrates a decoupling between seasonality and annual carbon cycle balance in northern ecosystems over 2015−2016, which is unprecedented in the past five decades of El Niño events.
Comparison of diametric and volumetric changes in Stanford type B aortic dissection patients in assessing aortic remodeling post-stent graft treatment.

Background The study aims to analyze the correlation between the maximal diameter (both axial and orthogonal) and volume changes in the true (TL) and false lumens (FL) after stent-grafting for Stanford type B aortic dissection. Method Computed tomography angiography was performed on 13 type B aortic dissection patients before and after procedure, and at 6 and 12 months follow-up. The lumens were divided into three regions: the stented area (Region 1), distal to the stent graft to the celiac artery (Region 2), and between the celiac artery and the iliac bifurcation (Region 3). Changes in aortic morphology were quantified by the increase or decrease of diametric and volumetric percentages from baseline measurements. Results At Region 1, the TL diameter and volume increased (pre-treatment: volume =51.4±41.9 mL, maximal axial diameter =22.4±6.8 mm, maximal orthogonal diameter =21.6±7.2 mm; follow-up: volume =130.7±69.2 mL, maximal axial diameter =40.1±8.1 mm, maximal orthogonal diameter =31.9+2.6 mm, P<0.05 for all comparisons), while FL decreased (pre-treatment: volume =129.6±150.5 mL; maximal axial diameter =43.0±15.8 mm; maximal orthogonal diameter =28.3±12.6 mm; follow-up: volume =66.6±95.0 mL, maximal axial diameter =24.5±19.9 mm, maximal orthogonal diameter =16.9±13.7, P<0.05 for all comparisons). Due to the uniformity in size throughout the vessel, high concordance was observed between diametric and volumetric measurements in the stented region with 93% and 92% between maximal axial diameter and volume for the true/false lumens, and 90% and 92% between maximal orthogonal diameter and volume for the true/false lumens. Large discrepancies were observed between the different measurement methods at regions distal to the stent graft, with up to 46% differences between maximal orthogonal diameter and volume. Conclusions Volume measurement was shown to be a much more sensitive indicator in identifying lumen expansion/shrinkage at the distal stented region.
Enhancing Self-Advocacy After Traumatic Brain Injury: A Randomized Controlled Trial

Objective: To evaluate the efficacy of a novel intervention aimed at enhancing self-advocacy in individuals living with traumatic brain injury (TBI). Setting: Community. Participants: Sixty-seven (35 allocated to treatment, 32 to control) community-dwelling adults 9 months or more post-TBI (mean of 8.9 years postinjury); previously discharged from inpatient or outpatient TBI rehabilitation; able to travel independently in the community, indicating a level of independence needed to engage in self-advocacy. Design: Longitudinal randomized 2-arm controlled trial (NCT no. 03385824). Computer-generated block randomization allocated participants to treatment/intervention or control/no-intervention. All outcome assessments completed by blinded study staff. Intervention: A manualized group intervention, Self-Advocacy for Independent Life (SAIL), addressing the self-efficacy beliefs, knowledge, and skills for self-advocacy following TBI. Main Outcome Measures: The Self-Advocacy Scale (SAS) (primary); General Self-Efficacy Scale (GSE); Personal Advocacy Activity Scale (PAAS); Satisfaction With Life Scale (SWLS). Results: The treatment group showed significantly greater improvement than controls from baseline to posttreatment on the primary measure (SAS) of self-efficacy specific to self-advocacy after TBI (effect size = 0.22). Similar improvements were found on secondary measures of general self-efficacy and satisfaction with life from baseline to posttreatment. However, significant between-groups gains for primary and secondary measures were not maintained over 6- and 12-week follow-up. Conclusions: Individuals living with chronic TBI sequelae can increase self-efficacy specific to self-advocacy, general self-efficacy, and satisfaction with life, through a TBI-specific intervention aimed at empowering individuals to advocate for their own needs and wishes. Sustaining gains over time may require ongoing community collaboration and support. This could involve community-based systems of self-advocacy education, resources, and peer support.
Prevalence and antibiotic susceptibility trends of periodontal pathogens in the subgingival microbiota of German periodontitis patients: A retrospective surveillance study.

OBJECTIVE This retrospective surveillance study aimed to follow periodontitis-associated bacterial profiles and to identify time-dependent changes in antibiotic susceptibility patterns. MATERIALS AND METHODS From 2008 to 2015 bacterial specimen from deep periodontal pockets were collected from a total of 7804 German adults diagnosed with periodontitis. Presence of selected bacteria was confirmed by anaerobic culture and nucleic acid amplification. Antimicrobial susceptibility of clinical isolates was tested by disk diffusion with antibiotics used for treatment of periodontitis and oral infections. Prevalences of periodontal pathogens were calculated and temporal evolution of antimicrobial susceptibility towards amoxicillin, amoxicillin/clavulanic acid, metronidazole, doxycycline, clindamycin, azithromycin, ciprofloxacin, and ampicillin was analyzed with logistic regression. RESULTS The prevalence of patients harboring bacteria was 95.9% Fusobacterium nucleatum, 88.0% Tannerella forsythia, 76.5% Treponema denticola, 76.4%, Campylobacter rectus, 76.0% Eikenella corrodens, 75.0% Capnocytophaga spp. , 68.2% Porphyromonas gingivalis, 57.7% Peptostreptococcus micros, 43.1% Prevotella intermedia, 30.4% Eubacterium nodatum and 21.5% Aggregatibacter actinomycetemcomitans. In 63.5 % of patients one or more isolates were not susceptible to at least one of the antibiotics tested. The data further revealed a trend towards decreasing susceptibility profiles (p < 0.05) with antibiotic non-susceptibilities in 37% of patients in 2008 and in 70% in 2015. CONCLUSIONS The present study confirmed a high prevalence of periodontal pathogens in the subgingival microbiota of German periodontitis patients. The data revealed an incremental increase in isolates displaying resistance to some antibiotics but no relevant change in susceptibility to amoxicillin and metronidazole.
Role for Mucin-5AC in Upper and Lower Airway Pathogenesis in Mice

Mucin-5AC (MUC5AC) is a major secreted mucin in pathogenic airways. To determine its role in mucus-related airway disorders, Muc5ac-deficient (Muc5ac−/− ) and wild-type (Muc5ac+/+ ) mice were compared in bleomycin-induced pulmonary fibrosis, respiratory syncytial virus (RSV) disease, and ozone toxicity. Significantly greater inflammation and fibrosis by bleomycin were developed in Muc5ac−/− lungs compared to Muc5ac+/+ lungs. More severe mucous cell metaplasia in fibrotic Muc5ac−/− lungs coincided with bronchial Muc2, Muc4, and Muc5b overexpression. Airway RSV replication was higher in Muc5ac−/− than in Muc5ac+/+ during early infection. RSV-caused pulmonary epithelial death, bronchial smooth muscle thickening, and syncytia formation were more severe in Muc5ac−/− compared to Muc5ac+/+ . Nasal septal damage and subepithelial mucoserous gland enrichment by RSV were greater in Muc5ac−/− than in Muc5ac+/+ . Ozone exposure developed more severe nasal airway injury accompanying submucosal gland hyperplasia and pulmonary proliferation in Muc5ac−/− than in Muc5ac+/+ . Ozone caused periodic acid-Schiff-positive secretion only in Muc5ac−/− nasal airways. Lung E-cadherin level was relatively lower in Muc5ac−/− than in Muc5ac+/+ basally and after bleomycin, RSV, and ozone exposure. Results indicate that MUC5AC is an essential mucosal component in acute phase airway injury protection. Subepithelial gland hyperplasia and adaptive increase of other epithelial mucins may compensate airway defense in Muc5ac−/− mice.
Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010–2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65–2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22–2.09) and non‐squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37–4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11–3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45–0.82, OR = 0.41, 95% CI 0.25–0.67, OR = 0.60, 95% CI 0.46–0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.
Caregiving for Parents Who Harmed You: A Conceptual Review

ABSTRACT Objectives: This paper aims to provide a conceptual review of prior research on the effect of a history of parental childhood maltreatment on the experiences and outcomes of adult-child caregivers who provide care to their perpetrating parents. Methods: We performed a search using several databases including PsycINFO, ScienceDirect, and Academic Search Premier (EBSCO) for relevant papers and reviewed reference sections of selected papers. Results: Histories of childhood maltreatment are associated with adverse psychological health in adult-child caregivers and reduced frequencies of providing support to their parents. The potential factors affecting the experiences and outcomes of such caregivers include contemporaneous relationships with perpetrating parents; caregivers’ sense of choice about providing care; opportunities for posttraumatic growth; and participating in care through the end of life. Conclusions: Caregiving for perpetrating parents can be particularly challenging due to complex, intersecting factors; thus, healthcare practitioners’ increased awareness of and knowledge about such caregivers are crucial to provide effective support. Clinical Implications: We highlighted the importance of ensuring caregivers’ sense of choice and assessing their posttraumatic growth. In caregiving at the end of life, we noted the importance of using a trauma-informed approach when interacting with caregivers and their family members during illness and bereavement.
Measuring Insulin Resistance in Humans

Background: Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use. Summary: In this historical perspective, we explore the evolution of the term “insulin resistance” and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity. We identify primary discoveries which were pivotal in expanding our knowledge of insulin resistance, the challenges in measurement and interpretation, contemporary techniques, and areas of future exploration. Key Message: Measurements of insulin resistance are important tools for defining and treating cardiometabolic diseases. Accurate quantification of this pathophysiological entity requires careful consideration of the assumptions and pitfalls of the methodological techniques and the historical and clinical context when interpreting and applying the results.
Prostate cancer patient‐derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens

Patient‐derived organoids (PDOs) represent promising preclinical models in various tumor types. In the context of prostate cancer (PCa), however, their establishment has been hampered by poor success rates, which impedes their broad use for translational research applications. Along with the necessity to improve culture conditions, there is a need to identify factors influencing outcomes and to determine how to assess success versus failure in organoid generation. In the present study, we report our unbiased efforts to generate PDOs from a cohort of 81 PCa specimens with diverse pathological and clinical features. We comprehensively analyzed histological features of each enrolled sample (Gleason score, tumor content, proliferation index) and correlated them with organoid growth patterns. We identified improved culture conditions favoring the generation of PCa organoids, yet no specific intrinsic tumor feature was broadly associated with sustained organoid growth. In addition, we performed phenotypic and molecular characterization of tumor–organoid pairs using immunohistochemistry, immunofluorescence, fluorescence in situ hybridization, and targeted sequencing. Morphological and immunohistochemical profiles of whole organoids altogether provided a fast readout to identify the most promising ones. Notably, primary samples were associated with an initial take‐rate of 83% (n = 60/72) in culture, with maintenance of cancer cells displaying common PCa alterations, such as PTEN loss and ERG overexpression. These cancer organoids were, however, progressively overgrown by organoids with a benign‐like phenotype. Finally, out of nine metastasis samples, we generated a novel organoid model derived from a hormone‐naïve lung metastasis, which displays alterations in the PI3K/Akt and Wnt/β‐catenin pathways and responds to androgen deprivation. Taken together, our comprehensive study explores determinants of outcome and highlights the opportunities and challenges associated with the establishment of stable tumor organoid lines derived from PCa patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.