Miracle-dz/UniFAR-FTUs huggingface dataset:
Serial assessment of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial.

AIMS We investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of stroke or systemic embolic events (S/SEE) and bleeding. METHODS AND RESULTS ENGAGE AF-TIMI 48 was a randomized trial of the oral factor Xa inhibitor edoxaban in patients with AF and a CHADS2 score of ≥2. We performed a nested prospective biomarker study in 6308 patients, analysing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/mL change), GDF-15 in 45.6% (≥300 pg/mL change) during 12 months. In a Cox regression model, upward changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE [adjusted hazard ratio (adj-HR) 1.74; 95% confidence interval (CI) 1.36-2.23 and adj-HR 1.27; 95% CI 1.07-1.50, respectively] and log2-transformed GDF-15 with bleeding (adj-HR 1.40; 95% CI 1.02-1.92). Reassessment of ABC-stroke (age, prior stroke/transient ischaemic attack, hsTnT, and NT-proBNP) and ABC-bleeding (age, prior bleeding, haemoglobin, hsTnT, and GDF-15) risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk [net reclassification improvement (NRI) 0.50; 95% CI 0.36-0.65; NRI 0.42; 95% CI 0.33-0.51, respectively]. CONCLUSION Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed that a substantial proportion of patients with AF had dynamic values. Greater increases in these biomarkers measured over 1 year are associated with important clinical outcomes in anticoagulated patients with AF.
Efficacy of Non-pharmacological Treatments on Emotional Symptoms of Children and Adults with Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis

Background: The present meta-analysis aimed to evaluate the efficacy of various non-pharmacological interventions on comorbid emotional symptoms such as depression, anxiety, and emotional dysregulation (ED) in children and adults with ADHD. Method: Forty-four randomized controlled trials (23 studies with ADHD children and 21 studies with ADHD adults) were included. Risk of bias, heterogeneity assessment, and subgroup analyses were conducted. Results: We found that therapies targeting the relationship between children and others (i.e., parent-training [on ED and depression] and social skills training [on ED]) were efficacious in the treatment of emotional symptoms in children with ADHD at post-intervention. As for adults with ADHD, cognitive behavioral therapy was found to be effective for the improvement of emotional symptoms at both post-intervention and follow-up. Conclusion: Our findings demonstrate that the efficacy of non-pharmacological interventions varies substantially across children and adults with ADHD. These results provide important implications for the selection of non-pharmacological interventions for children with ADHD.
The impact of the coronavirus disease and Tele-Heart Failure Clinic on cardiovascular mortality and heart failure hospitalization in ambulatory patients with heart failure

Background We sought to investigate the impact of the COVID-19 pandemic and the Tele-HF Clinic (Tele-HFC) program on cardiovascular death, heart failure (HF) rehospitalization, and heart transplantation rates in a cohort of ambulatory HF patients during and after the peak of the pandemic. Methods Using the HF clinic database, we compared data of patients with HF before, during, and after the peak of the pandemic (January 1 to March 17 [pre-COVID], March 17 to May 31 [peak-COVID], and June 1 to October 1 [post-COVID]). During peak-COVID, all patients were managed by Tele-HFC or hospitalization. After June 1, patients chose either a face-to-face clinic visit or a continuous tele-clinic visit. Results Cardiovascular death and medical titration rates were similar in peak-COVID compared with all other periods. HF readmission rates were significantly lower in peak-COVID (8.7% vs. 2.5%, p<0.001) and slightly increased (3.5%) post-COVID. Heart transplant rates were substantially increased in post-COVID (4.5% vs. peak-COVID [0%], p = 0.002). After June 1, 38% of patients continued with the Tele-HFC program. Patients managed by the Tele-HFC program for <6 months were less likely to have HF with reduced ejection fraction (73% vs. 54%, p = 0.005) and stage-D HF (33% vs. 14%, p = 0.001), and more likely to achieve the target neurohormonal blockade dose (p<0.01), compared with the ≥6-month Tele-HFC group. Conclusions HF rehospitalization and transplant rates significantly declined during the pandemic in ambulatory care of HF. However, reduction in these rates did not affect subsequent 5-month hospitalization and cardiovascular mortality in the setting of Tele-HFC program and continuum of advanced HF therapies.
Point-and-shoot: rapid quantitative detection methods for on-site food fraud analysis – moving out of the laboratory and into the food supply chain

Major food adulteration and contamination events occur with alarming regularity and are known to be episodic, with the question being not if but when another large-scale food safety/integrity incident will occur. Indeed, the challenges of maintaining food security are now internationally recognised. The ever increasing scale and complexity of food supply networks can lead to them becoming significantly more vulnerable to fraud and contamination, and potentially dysfunctional. This can make the task of deciding which analytical methods are more suitable to collect and analyse (bio)chemical data within complex food supply chains, at targeted points of vulnerability, that much more challenging. It is evident that those working within and associated with the food industry are seeking rapid, user-friendly methods to detect food fraud and contamination, and rapid/high-throughput screening methods for the analysis of food in general. In addition to being robust and reproducible, these methods should be portable and ideally handheld and/or remote sensor devices, that can be taken to or be positioned on/at-line at points of vulnerability along complex food supply networks and require a minimum amount of background training to acquire information rich data rapidly (ergo point-and-shoot). Here we briefly discuss a range of spectrometry and spectroscopy based approaches, many of which are commercially available, as well as other methods currently under development. We discuss a future perspective of how this range of detection methods in the growing sensor portfolio, along with developments in computational and information sciences such as predictive computing and the Internet of Things, will together form systems- and technology-based approaches that significantly reduce the areas of vulnerability to food crime within food supply chains. As food fraud is a problem of systems and therefore requires systems level solutions and thinking.
A Non‐Local Richards Equation to Model Unsaturated Flow in Highly Heterogeneous Media under Nonequilibrium Pressure Conditions

This paper presents an upscaled model for unsaturated flow in highly heterogeneous media. Flow in the highly conductive domain is described with Richards' equation, while water exchange with poorly conductive blocks is captured by a non‐local sink term with a diffusive memory kernel. The model is tested with a numerical test case.
Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond

ABSTRACT Introduction Despite the substantial improvements made in human epidermal growth factor receptor 2 (HER2)–targeted therapies since the approval of trastuzumab more than 20 years ago, there is still considerable unmet need in patients with HER2-expressing breast cancer (BC) and other solid tumors. Trastuzumab deruxtecan (T-DXd) is a newer antibody-drug conjugate approved for the treatment of metastatic breast cancer (BC) and gastric cancer (GC) and is under active investigation in other solid tumors, including non–small cell lung cancer, colorectal cancer, and HER2-low tumors. Areas covered The current treatment and investigational landscape of HER2-positive and HER2-low metastatic BC (mBC) and the preclinical and clinical trials investigating T-DXd. To identify relevant literature, a search was performed on English-language publications and congress abstracts. Expert opinion T-DXd is likely to become the standard of care for second-line treatment of HER2-positive mBC, and it may play a role in the treatment of hormone receptor–positive and triple-negative mBC with HER2-low expression. Because it was recently approved in the United States and Japan to treat HER2-positive metastatic GC, it holds promise for the treatment of other HER2-positive solid tumors, including colorectal cancer, non–small cell lung cancer, and HER2-low BC.
Fatality and risk features for prognosis in COVID-19 according to the care approach – a retrospective cohort study

Introduction This study analyzed the impact of a categorized approach, based on patients’ prognosis, on major outcomes and explanators in patients hospitalized for COVID-19 pneumonia in an academic center in Spain. Methods Retrospective cohort study (March 3 to May 2, 2020). Patients were categorized according to the followed clinical management, as maximum care or limited therapeutic effort (LTE). Main outcomes were all-cause mortality and need for invasive mechanical ventilation (IMV). Baseline factors associated with outcomes were analyzed by multiple logistic regression, estimating odds ratios (OR; 95%CI). Results Thirty-hundred and six patients were hospitalized, median age 65.0 years, 57.8% males, 53.3% Charlson index ≥3. The overall all-cause fatality rate was 15.0% (n = 46). Maximum care was provided in 238 (77.8%), IMV was used in 38 patients (16.0%), and 5.5% died. LTE was decided in 68 patients (22.2%), none received IMV and fatality was 48.5%. Independent risk factors of mortality under maximum care were lymphocytes <790/mm3, troponin T >15ng/L and hypotension. Advanced age, lymphocytes <790/mm3 and BNP >240pg/mL independently associated with IMV requirement. Conclusion Overall fatality in the cohort was 15% but markedly varied regarding the decided approach (maximum care versus LTE), translating into nine-fold higher mortality and different risk factors.
Compartmentalization of Melanin Biosynthetic Enzymes Contributes to Self-Defense against Intermediate Compound Scytalone in Botrytis cinerea

The devastating gray mold pathogen Botrytis cinerea propagates via melanized conidia and sclerotia. This study reveals that the sclerotial germination of B. cinerea is differentially affected by different enzymes in the melanin synthesis pathway. ABSTRACT In filamentous fungi, 1,8-dihydroxynaphthalene (DHN) melanin is a major component of the extracellular matrix, endowing fungi with environmental tolerance and some pathogenic species with pathogenicity. However, the subcellular location of the melanin biosynthesis pathway components remains obscure. Using the gray mold pathogen Botrytis cinerea, the DHN melanin intermediate scytalone was characterized via phenotypic and chemical analysis of mutants, and the key enzymes participating in melanin synthesis were fused with fluorescent proteins to observe their subcellular localizations. The Δbcscd1 mutant accumulated scytalone in the culture filtrate rather than in mycelium. Excessive scytalone appears to be self-inhibitory to the fungus, leading to repressed sclerotial germination and sporulation in the Δbcscd1 mutant. The BcBRN1/2 enzymes responsible for synthesizing scytalone were localized in endosomes and found to be trafficked to the cell surface, accompanied by the accumulation of BcSCD1 proteins in the cell wall. In contrast, the early-stage melanin synthesis enzymes BcPKS12/13 and BcYGH1 were localized in peroxisomes. Taken together, the results of this study revealed the subcellular distribution of melanin biosynthetic enzymes in B. cinerea, indicating that the encapsulation and externalization of the melanin synthetic enzymes need to be delicately orchestrated to ensure enzymatic efficiency and protect itself from the adverse effect of the toxic intermediate metabolite. IMPORTANCE The devastating gray mold pathogen Botrytis cinerea propagates via melanized conidia and sclerotia. This study reveals that the sclerotial germination of B. cinerea is differentially affected by different enzymes in the melanin synthesis pathway. Using gene knockout mutants and chemical analysis, we found that excessive accumulation of the melanin intermediate scytalone is inhibitory to B. cinerea. Subcellular localization analysis of the melanin synthesis enzymes of B. cinerea suggested two-stage partitioning of the melanogenesis pathway: the intracellular stage involves the steps until the intermediate scytalone was translocated to the cell surface, whereas the extracellular stage comprises all the steps occurring in the wall from scytalone to final melanin formation. These strategies make the fungus avert self-poisoning during melanin production. This study opens avenues for better understanding the mechanisms of secondary metabolite production in filamentous fungi.
Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.
Precipitation of Curcuminoids from Hydrotrope Solution: Crystal Nucleation and Growth Kinetics from Batch Experiments

Precipitation kinetics of curcuminoids from aqueous hydrotropic solutions of sodium cumene sulfonate was investigated in a laboratory‐scale agitated vessel using acidic water (pH 3) as a precipitant. The time evolution of the crystal size distribution was used to deduce simultaneously the crystal growth kinetics. The transient population density curves were measured by a Coulter counter light scattering unit. The kinetic data from the experimental runs were correlated by a power law relative kinetic expression. Crystallization experiments using hydrotropic extracts of turmeric were also performed to compare the results with pure curcuminoids in the hydrotrope solutions. The results indicate slow crystal growth and thus formation of very fine crystals of curcuminoids in the range of 1 to 100 µm.
Assessing the risk of venous thromboembolism (VTE) in ambulatory patients with cancer: Rationale and implementation of a pharmacist-led VTE risk assessment program in an ambulatory cancer centre

Objectives The objectives of this paper were to identify and compare clinical prediction models used to assess the risk of venous thromboembolism (VTE) in ambulatory patients with cancer, as well as review the rationale and implementation of a pharmacist-led VTE screening program using the Khorana Risk Score model in an ambulatory oncology centre in Sault Ste. Marie, Ontario, Canada. Data Sources PubMed was used to identify clinical practice guidelines and review articles discussing risk prediction models used to assess VTE risk in ambulatory patients with cancer. Data Summary Three commonly used VTE risk prediction models in ambulatory patients with cancer: the Khorana Risk Score, Vienna Cancer and Thrombosis Study (CATS) and Protecht Score, were identified via literature review. After considering guideline recommendations, site-specific factors (i.e. laboratory costs, time pharmacists spent calculating VTE risk) and evidence from the CASSINI and AVERT trials, a novel pharmacist-led VTE risk assessment program using the Khorana Risk Score was developed during a fourth-year PharmD clinical rotation at the Algoma District Cancer Program (ADCP) [ambulatory cancer care centre]. ADCP patients with a Khorana Risk Score of ≥ 2 were referred to the hematologist for a full VTE workup. Considering limitations, inclusion and exclusion criteria of the CASSINI and AVERT trials, the hematologist and pharmacy team decided on appropriate initiation of thromboprophylaxis with a direct oral anticoagulant (DOAC). Conclusions The Khorana Risk Score was the chosen model used for the pharmacist-led VTE risk assessment program due to its user-friendly scoring algorithm, evidence from validation studies and clinical trials, as well as ease of integration into pharmacy workflow. More research is needed to determine if pharmacist-led VTE risk assessment programs will impact patient outcomes, such as morbidity and mortality, secondary to cancer-associated thrombosis.
Revisiting Shyness and Sociability in Schizophrenia: A Psychometric Examination of Measurement Invariance and Mean Level Differences

Abstract Although there is a long and rich empirical history of demonstrating differences on psychological self-report measures between people with schizophrenia and healthy controls, the question of whether both groups respond to psychological measures in the same way has gone largely unexplored. That is, is there measurement equivalence, or invariance, across the samples? To our knowledge, there have been no published studies on measurement equivalency in personality measures across groups diagnosed with and without schizophrenia. Here we examined the question of measurement invariance on two widely used questionnaires assessing temperament, the Cheek and Buss Shyness and Sociability Scales (CBSHY and CBSOC, respectively) between 147 stable adult outpatients with schizophrenia and 147 healthy age- and sex-matched controls. Results supported measurement invariance of the CBSHY and CBSOC across our clinical and non-clinical groups. These findings suggested that stable adult outpatients with schizophrenia and age- and sex-matched controls respond to the shyness and sociability items in the same way. We found that adults with schizophrenia reported higher levels of shyness and lower levels of sociability than healthy controls, consistent with prior studies. Findings are discussed concerning their relevance more broadly to self-report assessments of personality and psychological traits in clinical populations.
Effect of foliar fertilization application on the growth and mineral nutrient content of maize seedlings under drought and salinity

Abstract The objective of the present study was to investigate the interactive effects of foliar fertilization and drought and salinity on the growth of maize. Maize plants were grown in soil under drought or salinity in a greenhouse for 23 days after sowing. At harvest, plant height, shoot biomass, and the lengths, fresh weights and dry weights of the blade in the expanded leaf 3 and expanding leaves 4 and 5 were determined. Mineral elements (Na, K, Ca, Mg, P and N) in individual leaves were analyzed. Although there was a reduction in evapotranspiration, maize growth, such as shoot fresh weight and dry weight, and leaf fresh weight and dry weight under drought and salinity, the application of foliar fertilization did not improve plant growth under short-term drought or salt stress. Drought reduced the uptake of K, Ca, Mg and P, which may be attributed to decreased transpiration. An increase or no change in the nutrient concentration in leaves under saline conditions suggests that an osmotic effect may be responsible for the plant reduction.
Low-Temperature-Processible, Transparent, and Air-Operable n-Channel Fluorinated Phenylethylated Naphthalenetetracarboxylic Diimide Semiconductors Applied to Flexible Transistors

New N,N′-disubstituted-1,4,5,8-naphthalene tetracarboxylic acid diimides (NTCDI) with fluorinated phenylethyl groups were synthesized. In particular, N,N′-bis(2-(pentafluorophenyl)ethyl)-1,4,5,8-naphthalene tetracarboxylic acid diimide (5FPE-NTCDI) showed high electron mobility, more than 0.1 cm2/(V s) in air, even though the film was deposited at room temperature. The correlation of the crystallinity, morphology, and mobility with the substrate temperature during deposition (Tsub) was studied using X-ray diffraction (XRD) and atomic force microscopy (AFM). The films of 5FPE-NTCDI exhibited a “thin film phase”, mixed phase, and crystal bulk phase as Tsub was increased. The mixed phase on an octadecyltrimethoxysilane (OTS)-treated substrate also has high electron mobility due to well connected long fiber-shaped grains. The high mobility at low Tsub has enabled fabrication of flexible transistors on the clear plastic substrate poly(ethylene terephthalate) (PET). The highest mobility for a flexible, transpar.
Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates

Abstract Objective Perimenopause is associated with declines in attention, working memory and verbal memory; however, there are significant individual differences. Further, the contributions of hormones and menopausal symptoms to domain-specific cognitive functions remain unknown. This longitudinal study aimed to determine whether there were distinct cognitive profiles in perimenopause and to identify factors associated with each profile. Design In a sample of 85 women evaluated over 400 bi-annual visits, we administered a comprehensive neuropsychological battery, assessed menopausal symptoms and measured 17β-estradiol and follicle stimulating hormone. Multilevel latent profile analysis was used to identify cognitive profiles. Regressions were conducted to determine differences in hormones and symptoms by profile after adjusting for Stages of Reproductive Aging Workshop + 10 (STRAW + 10) stage and demographic factors. Results Perimenopausal cognitive profiles consisted of cognitively normal (Profile 1; n = 162), weaknesses in verbal learning and memory (Profile 2; n = 94), strengths in verbal learning and memory (Profile 3; n = 98) and strengths in attention and executive function (Profile 4; n = 61). Profile 2 was differentiated by less hormonal variability and more sleep disturbance than Profile 1 (p < 0.05). Conclusions There is significant heterogeneity in cognition during perimenopause. While most women do not develop impairments, a significant minority experience weaknesses in verbal learning and memory. Profile analysis may identify at-risk populations and inform interventions.