Miracle-dz/UniFAR-FTUs huggingface dataset:
A nurse practitioner–led care bundle approach for primary care of patients with complex health needs

ABSTRACT Background: Often developed for acute care and less frequently for primary care, care bundles are clusters of evidence-based practices for improving care delivery and patient outcomes. Care bundles usually arise when ineffective or costly outcomes are identified, are meant to make care more reliable, and require superb teamwork and communication. Local problem: Patients using the highest proportion of health care services are those living with complex health conditions and challenging sociocultural lives, statistics corroborated within our primary care clinic. In our nurse practitioner (NP)-led, interprofessional, team-based primary care program serving mainly low-income patients, we noted that many patients with multiple chronic conditions had an excess of clinic encounters, emergency department visits, and hospitalizations. Methods: To improve health status for these patients and reduce costly care inefficiencies, we developed a unique bundle of care practices for embedding within our NP-led complex care program. Our goals were to improve patient efficacy for self-management of chronic conditions and promote appropriate use of health care resources and services. Interventions: Using AEIØOU as a mnemonic, the derived care bundle better focused our team efforts and provided us with a planning, communication, and documentation schema for quality improvement. It was particularly useful for team-based care because tasks could be documented or communicated by letter or number and easily reviewed by team members or others involved in patients' care. Results: Use of the AEIØOU bundle within our program resulted in better coordination of team-based comprehensive care for our high-needs patients, seen anecdotally in fewer unnecessary contacts and missed appointments and in patient appreciation comments. Emergency department visits and hospitalization data for the six months before compared with 6 months after enrollment in the program showed significant reductions. Conclusions: To improve the primary care of complex patient populations, we recommend further use and testing of the AEIØOU bundle within other care models.
Prognostic Values of the Timing of Antibiotic Administration and the Sepsis Bundle Component in Elderly Patients With Septic Shock: A Retrospective Study

Supplemental Digital Content is available in the text ABSTRACT Introduction: Elderly patients are more susceptible to sepsis and septic shock. Early administration of broad-spectrum antibiotics is a key element of the sepsis management of bundle. Our study aimed to investigate the association between the timing of antibiotics administration and the risk of adverse outcomes in elderly patients with septic shock, and to examine the prognostic value of other bundle elements. Method: This is a single-center, retrospective, case-control study including elderly patients (aged ≥ 65 years) diagnosed with septic shock in the emergency department between October 1, 2018, and December 31, 2019. Eligible patients were divided into early (within 1 h) and late (beyond 1 h) groups according to the time interval between septic shock recognition and initial antibiotic administration. The characteristics, sepsis-related severity scores, management strategy, and outcomes were recorded. A multivariate logistic regression model was used to identify the independent prognostic factors. Results: A total of 331 patients were included in the study. The overall 90-day mortality rate was 43.8% (145/331). There were no significant differences in baseline characteristics, sepsis-related severity scores, and management strategy between the two groups. There was no significant difference between the early and late groups in the rate of intensive care unit transfer (46.4% vs. 46.6%, P = 0.96), endotracheal intubation (28.3% vs. 27.5%, P = 0.87), renal replacement therapy (21.7% vs. 21.8%, P = 1.00), or 90-day mortality (44.2% vs. 43.5%, P = 0.90). Serum lactate level (hazard ratio [HR] = 1.15, P < 0.01) and source control (HR = 0.56, P = 0.03) were identified as independent factors associated with 90-day mortality. Conclusion: The timing of antibiotic administration was not associated with adverse outcomes in elderly patients with septic shock. Serum lactate level and source control implementation were independent prognostic factors in these patients.
Weakly supervised annotation‐free cancer detection and prediction of genotype in routine histopathology

Deep learning is a powerful tool in computational pathology: it can be used for tumor detection and for predicting genetic alterations based on histopathology images alone. Conventionally, tumor detection and prediction of genetic alterations are two separate workflows. Newer methods have combined them, but require complex, manually engineered computational pipelines, restricting reproducibility and robustness. To address these issues, we present a new method for simultaneous tumor detection and prediction of genetic alterations: The Slide‐Level Assessment Model (SLAM) uses a single off‐the‐shelf neural network to predict molecular alterations directly from routine pathology slides without any manual annotations, improving upon previous methods by automatically excluding normal and non‐informative tissue regions. SLAM requires only standard programming libraries and is conceptually simpler than previous approaches. We have extensively validated SLAM for clinically relevant tasks using two large multicentric cohorts of colorectal cancer patients, Darmkrebs: Chancen der Verhütung durch Screening (DACHS) from Germany and Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR‐BCIP) from the UK. We show that SLAM yields reliable slide‐level classification of tumor presence with an area under the receiver operating curve (AUROC) of 0.980 (confidence interval 0.975, 0.984; n = 2,297 tumor and n = 1,281 normal slides). In addition, SLAM can detect microsatellite instability (MSI)/mismatch repair deficiency (dMMR) or microsatellite stability/mismatch repair proficiency with an AUROC of 0.909 (0.888, 0.929; n = 2,039 patients) and BRAF mutational status with an AUROC of 0.821 (0.786, 0.852; n = 2,075 patients). The improvement with respect to previous methods was validated in a large external testing cohort in which MSI/dMMR status was detected with an AUROC of 0.900 (0.864, 0.931; n = 805 patients). In addition, SLAM provides human‐interpretable visualization maps, enabling the analysis of multiplexed network predictions by human experts. In summary, SLAM is a new simple and powerful method for computational pathology that could be applied to multiple disease contexts. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Physicochemical and Bioactive Characteristics of Wild Grown Bilberry (Vaccinium myrtillus L.) Genotypes from Northeastern Turkey

In present study, fruit weight, fruit firmness, external fruit color, soluble solid content, pH, titratable acidity, vitamin C, total phenolics, total anthocyanins, and antioxidant capacity of eight wild bilberry grown in Coruh valley in northeastern Turkey were determined. The blueberry cv. ‘Bluecrop’ is also included study to make comparison with bilberry genotypes. Antioxidant activity of bilberry and blueberry fruits were comparatively assessed by FRAP (Ferric reducing antioxidant power) assay. Significantly higher content of phenolics and anthocyanins was found in bilberry fruits than in blueberry fruits. However blueberry cv. ‘Bluecrop’ exhibited higher fruit weight and vitamin C content than bilberry fruits. Total phenolic and total anthocyanin content was 327 mg gallic acid equivalent and 142 mg of cyanidin-3-glucoside equivalent in 100 g fresh fruit in cv. ‘Bluecrop’ while it was between 492-563 mg gallic acid equaivalent and 307-342 mg of cyanidin-3-glucoside equivalent in 100 g fresh fruits of bilberry accessions. Moreover, wild accessions approximately had 2-3 folds higher antioxidant capacity than cv. ‘Bluecrop’. Results suggest the possibility of improving the bioactive and antioxidant properties of bilberry cultivars based food products by using wild ones in cross breeding. It was also concluded that genotypes significantly affect their bioactive content and consequently the possibility of using wild bilberry fruits as a potential source of natural antioxidants in food industry.
Identification of independent risk factors for diabetic neuropathy progression in patients with type 2 diabetes mellitus

Objective To identify independent risk factors for diabetic neuropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods We retrospectively analyzed 376 patients with T2DM at the First Affiliated Hospital of Fujian Medical University, China between January 2013 and October 2016. Multivariate logistic regression was used to explore potential risk factors for progression of DN in patients with T2DM. Effect sizes were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). Results The prevalence of DN in patients with T2DM was 43.1%. Multivariate logistic regression indicated that retinopathy (OR: 2.755, 95% CI: 1.599–4.746); diabetic nephropathy (OR: 2.196, 95% CI: 1.279–3.772); longer duration of T2DM (OR: 1.081, 95% CI: 1.045–1.120); use of insulin (OR: 1.091, 95% CI: 1.018–1.170); longer history of alcohol consumption (OR: 1.034, 95% CI: 1.010–1.059); and higher blood urea nitrogen (OR: 1.081, 95% CI: 1.009–1.159) were associated with increased risk of DN in patients with T2DM. Conclusions Retinopathy, diabetic nephropathy, longer duration of T2DM, use of insulin, longer history of alcohol consumption, and higher blood urea nitrogen were independent risk factors for DN. These findings should be verified in large-scale prospective studies.
Morphological characteristics of eyes with neovascular age-related macular degeneration and good long-term visual outcomes after anti-VEGF therapy

Purpose To analyse the morphological characteristics of eyes with neovascular age-related macular degeneration (AMD) with good long-term visual acuity after anti-VEGF (vascular endothelial growth factor) therapy. Methods Retrospective, observational study of 175 patients with neovascular AMD with >5 years of follow-up after initiating anti-VEGF therapy. Spectral-domain optical coherence tomography images were assessed for thickness of pigment epithelial detachment (PED), subretinal hyper-reflective material (SHRM), subretinal fluid and subfoveal choroidal, as well as the integrity of the outer retinal bands. Results The final analysis cohort included 203 eyes (175 patients) followed for a mean of 7.84±1.70 years (range: 5–11). The maximum PED thickness in the foveal central subfield (FCS) was significantly lower (p<0.001) in the poor vision group (13.11 μm) compared with the intermediate (86.25 μm) or good (97.92 μm) vision groups, respectively. In contrast, the maximum thickness of SHRM in the FCS was significantly thicker (p<0.001) in eyes with poor vision (149.46 μm) compared with eyes with intermediate vision (64.37 μm) which in turn were significantly thicker (p<0.001) than eyes with good vision (9.35 μm). The good vision group also had better continuity of all outer retinal bands (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) compared with the other two groups (all p<0.001). Conclusion A thicker PED and thinner SHRM were correlated with better vision in eyes with neovascular AMD following long-term anti-VEGF therapy. If replicated in future prospective studies, these findings may have implications for design of optimal anatomic endpoints for neovascular AMD treatment.
cGAS-STING-mediated IFNI Response in Host Defense and Neuroinflammatory Diseases

The presence of foreign or misplaced nucleic acids is a dangerous signal that triggers innate immune responses by activating cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and binding to its downstream signaling effector stimulator of interferon genes (STING). Then the cGAS-STING pathway activation links nucleic acid-sensing to immune responses and pathogenic entities clearance. However, the overactivation of this signaling pathway leads to fatal immune disorders and contributes to the progression of many human inflammatory diseases. Therefore, optimal activation of this pathway is crucial for the elimination of invading pathogens and the maintenance of immune homeostasis. In this review, we will summarize its fundamental roles in initiating host defense against invading pathogens and discuss its pathogenic roles in multiple neuro-inflammatory diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and other neurodegenerative diseases.
Clinico-radiological and biochemical clues to early diagnosis of mucolipidosis type II

Mucolipidosis type II or inclusion cell disease (I-cell) disease is a rare autosomal recessive lysosomal storage disorder caused by deficiency of N-actelyglucosamine-1phosphotransferase alpha/beta. The disease manifests in utero with short, bent long bones and periosteal cloaking evident at birth. We describe the clinical features in three neonates and allude to the key skeletal and biochemical manifestations to suspect mucolipidosis II, and further confirm the diagnosis by appropriate enzyme testing. As some of these features are transient, early identification and suspicion are important to diagnose mucolipidosis II in the neonatal period.
HLM-beads: Rapid Assessment of Nonspecific Binding to Human Liver Microsomes Using Magnetizable Beads

In early drug development, drug-drug interaction risk is routinely assessed using human liver microsomes (HLMs). Nonspecific binding of drugs to HLMs can affect the determination of accurate enzyme parameters (Km, Ki, KI). Previously, we described a novel in vitro model consisting of HLMs bound to magnetizable beads [HLM-magnetizable-beads system (HLM-beads)]. The HLM-beads enable rapid separation of HLMs from incubation media by applying a magnetic field. Here, HLM-beads were further characterized and evaluated as a tool to assess HLM nonspecific binding of small molecules. The free fractions (fu,mic) of 13 compounds (chosen based on their pKa values) were determined using HLM-beads under three HLM concentrations (0.025, 0.50, and 1.0 mg/ml) and compared with those determined by equilibrium dialysis. Most fu,mic values obtained using HLM-beads were within 0.5- to 2-fold of the values determined using equilibrium dialysis. The highest fold difference were observed for high binders itraconazole and BIRT2584 (1.9- to 2.9-fold), as the pronounced adsorption of these compounds to the equilibrium dialysis apparatus interfered with their fu,mic determination. Correlation and linear regression analysis of the fu,mic values generated using HLM-beads and equilibrium dialysis was conducted. Overall, a good correlation of fu,mic values obtained by the two methods were observed, as the r and R2 values from correlational analysis and linear regression analysis were >0.9 and >0.89, respectively. These studies demonstrate that HLM-beads can produce comparable fu,mic values as determined by equilibrium dialysis while reducing the time required for this type of study from hours to only 10 minutes and compound apparatus adsorption. SIGNIFICANCE STATEMENT This work introduces a new method of rapidly assessing nonspecific microsomal binding using human liver microsomes bound to magnetizable beads.
Safety and efficacy of using heat-killed Lactobacillus plantarum L-137: High-dose and long-term use effects on immune-related safety and intestinal bacterial flora

Abstract Heat-killed Lactobacillus plantarum L-137 (HK L-137) promotes immune function in animals. In healthy people, T-cell proliferation was shown to be enhanced by taking 10 mg HK L-137 daily for 12 weeks. However, the safety and efficacy of higher doses or longer treatments have not yet been investigated in humans. To investigate the high-dose and long-term use effects of HK L-137 on immune-related safety and on host intestinal bacterial flora, 15 healthy volunteers took a daily HK L-137 (50 mg) preparation for 4 weeks. An additional 29 participants who regularly visited a clinic for health care took HK L-137 (10 mg) daily for 12 months. Measures for anthropometrics, hematology, biochemistry, and urinalysis were taken at scheduled timepoints for all participants. Stool and blood samples were also collected and evaluated for microbes and short-chain fatty acids (SCFA); isolated T-cells were assessed for levels of proliferation induced by phytohemagglutinin in the long-term study. Adverse events or shifts in clinical measures from normal ranges due to the dietary intervention were not observed in the high-dose or long-term studies. Long-term intake also did not result in immune exhaustion due to any chronic immunostimulation; ex vivo T-cell proliferation was significantly greater at 12 months than at baseline (p < 0.01). In addition, the Firmicutes/Bacteroidetes ratio in stool samples was significantly lower at 12 months than at baseline (p < 0.05) due to the long-term intake of the HK L-137. Lastly, fecal SCFA concentrations were significantly greater (p < 0.05) at 6 months than at baseline. From these data, it can be concluded that the efficacy of HK L-137 is maintained with no overt adverse effects as a result of high-dose and/or long-term consumption.
Preparation of low-cost perovskite solar cells with high-quality perovskite films in an ambient atmosphere

High-quality perovskite films are extremely crucial to obtain perovskite solar cells with excellent photovoltaic performance, especially for carbon-based hole transport materials (HTM)-free perovskite solar cells. In this work, a facile and low-cost double two-step method (DT-method) is developed to prepare uniform and pinhole-free CH3NH3PbI3 perovskite films in an ambient atmosphere by utilizing the dissolution-recrystallization of PbI2 in DMF. That is to spin-coat PbI2 and CH3NH3I solution sequentially onto pristine perovskite films prepared by the conventional two-step method. The solar cells fabricated by the DT-method show a dramatic performance improvement, including V oc, J sc, and fill factor reach 0.85 V, 15.56 mA cm−2, and 0.58 respectively, which increase power conversion efficiency from 3.93% to 7.58% compared with the conventional two-step method. The improvement in performance and stability of solar cells is mainly due to the higher coverage of perovskite films onto the underlying mesoporous TiO2 layer and a negligible amount of PbI2 residue, which can effectively reduce charge recombination and promote the rapid transfer of charge carriers. In summary, this work presents a process for preparing carbon-based HTM-free perovskite solar cells (PSCs) in a high-humidity atmospheric environment (60%–85%). This simple device structure and preparation condition can greatly reduce the production threshold and cost of PSCs.
Effects of Ankle-Foot Orthoses on acceleration and energy cost of walking in children and adolescents with cerebral palsy

Background: Impaired postural control is a key feature of cerebral palsy that affects daily living. Measures of trunk movement and acceleration have been used to assess dynamic postural control previously. In many children with cerebral palsy, ankle-foot orthoses are used to provide a stable base of support, but their effect on postural control is not yet understood. Objectives: The objectives of the current study were to investigate the effects of ankle-foot orthoses on postural control and energy cost of walking in children with cerebral palsy. Study design: Clinical study with controls. Methods: Trunk accelerometry (amplitude and structure) and energy cost of walking (J/kg/m) were recorded from five-minute walking trials with and without ankle-foot orthoses for children with cerebral palsy and without orthoses for the reference group. Results: Nineteen children with unilateral spastic cerebral palsy and fourteen typically developed children participated. The use of ankle-foot orthoses increased structure complexity of trunk acceleration in mediolateral and anterior–posterior directions. The use of ankle-foot orthoses changed mediolateral-structure toward values found in typically developed children. This change was not associated with a change in energy cost during walking. Conclusions: The use of ankle-foot orthoses does affect trunk acceleration that may indicate a beneficial effect on postural control. Using measures of trunk acceleration may contribute to clinical understanding on how the use of orthoses affect postural control.
Sport Participation and Academic Performance in Children and Adolescents: A Systematic Review and Meta-analysis

Supplemental digital content is available in the text. ABSTRACT Introduction Physical activity can improve academic performance; however, much less is known about the specific association between sport participation and academic performance, and this evidence has not been synthesized. Our aim was to systematically review and combine via meta-analyses evidence of the association between sport participation and academic performance in children and adolescents. Methods We conducted searches of five electronic databases using sport and academic performance related terms. We combined evidence from eligible studies using a structural equation modeling approach to multilevel meta-analysis. Results From 115 eligible studies, most of which had a high risk of bias (k = 87), we meta-analyzed 298 effect sizes. Overall, sport participation had a small positive effect on academic performance (d = 0.26, 95% confidence interval = 0.09, 0.42). Moderator analyses indicated that sports participation was most beneficial for academic performance when it was at a moderate dose (i.e., 1–2 h·wk−1), compared with no sport or a high dose of sport (3+ h·wk−1). Conclusions Sports participation during school hours was more beneficial for academic performance compared with sport participation outside school hours. Based on mostly low-quality studies, we found some evidence that sport could positively affect academic performance in children and adolescents. It appears that sport participation of a moderate dose and at school could be used to promote academic performance. However, if this field were to inform policy, high-quality studies are needed that provide insight into the effect of dose and sport characteristics on academic performance.