Miracle-dz/UniFAR-FTUs huggingface dataset:
Nose-to-Brain Delivery by Nanosuspensions-Based in situ Gel for Breviscapine

Purpose Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood–brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity. Materials and Methods Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats. Results The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively. Conclusion It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.
Calf Circumference as an Optimal Choice of Four Screening Tools for Sarcopenia Among Ethnic Chinese Older Adults in Assisted Living

Introduction Sarcopenia is highly prevalent among residents of assisted-living facilities. However, the optimal screening tools are not clear. Therefore, we compared the performance of four recommended screening tools for predicting sarcopenia. Methods The study recruited 177 people over 65 years of age in assisted-living facilities. Appendicular muscle mass index was measured using bioelectrical impedance analysis. Calf circumference (CC), handgrip, six-meters walking speed, and screening questionnaires including SARC-CalF, SARC-F and 5-item Mini Sarcopenia Risk Assessment (MSRA-5) were evaluated. The diagnosis criteria for sarcopenia were based on the Asian Working Group for Sarcopenia 2019 consensus. The area under the receiver operating characteristic curves (AUC) was used to contrast the diagnostic accuracy of screening tools. Results The prevalence of sarcopenia was 52.7% among men and 51.2% among women. After adjusting for age, sex, body mass index and SARC-CalF score, CC remained significantly associated with sarcopenia in logistic regression analysis. The prediction model for sarcopenia based on CC alone had the highest accuracy compared to SARC-CalF, MSRA-5 and SARC-F (AUC, 0.819 vs 0.734 vs 0.600 vs 0.576; sensitivity/specificity, 80.4%/71.8% vs 38.0%/80.0% vs 60.7%/54.2% vs 10.9%/91.8%). Differences in AUCs between the prediction models were statistically significant (CC vs. SARC-CalF, P = 0.0181; SARC-CalF vs. MSRA-5, P = 0.0042). Optimal cutoff values for predicting sarcopenia were CC <34 cm in men and <33 cm in women. Conclusion To predict sarcopenia based on low CC alone is accurate, easy and inexpensive for use in assisted-living facility settings. Further validation studies in different populations are suggested.
Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies

Calculating the sample size in scientific studies is one of the critical issues as regards the scientific contribution of the study. The sample size critically affects the hypothesis and the study design, and there is no straightforward way of calculating the effective sample size for reaching an accurate conclusion. Use of a statistically incorrect sample size may lead to inadequate results in both clinical and laboratory studies as well as resulting in time loss, cost, and ethical problems. This review holds two main aims. The first aim is to explain the importance of sample size and its relationship to effect size (ES) and statistical significance. The second aim is to assist researchers planning to perform sample size estimations by suggesting and elucidating available alternative software, guidelines and references that will serve different scientific purposes.
Prospective Evaluation of Association Between Negative Emotions and Heart Failure Symptom Severity

Background Prior studies of symptoms in heart failure (HF) were largely cross-sectional and symptoms were measured using retrospective recall. Because negative emotions influence information processing, retrospective symptom reports by patients with depressive symptoms and anxiety may be biased. The purpose of this study was to determine whether there are differences in patterns of symptom changes, measured prospectively, over 15 days by levels of depressive symptoms and anxiety. Methods HF patients (N=52) rated daily symptom severity for shortness of breath (SOB), fatigue, sleep disturbance, and edema over 15 days on a 10-point visual analogue scale. Patients were grouped into higher vs lower levels of depressive symptoms and anxiety, respectively, based on median scores of Brief Symptom Inventory subscales. Latent growth curve modeling was used to examine whether patterns of symptom changes over 15 days differed in higher vs lower levels of depressive symptom and anxiety groups. Results Those in the higher depressive symptom group had lower levels of baseline symptom severity in SOB (β: −1.46), fatigue (β: −1.71), sleep disturbance (β: −1.78), and edema (β: −1.97) than those in the lower depressive symptom group. However, there were no significant differences in rates of changes in the severity of any of the four symptoms between groups. Anxiety was not associated with baseline severity of symptoms or rates of changes in any of the four symptoms. Conclusion Depressive symptoms, but not anxiety, were associated with daily symptom experience. HF patients with higher levels of depressive symptoms may perceive their symptom severity differently than patients with lower levels of depressive symptoms.
The potential of tumour microenvironment markers to stratify the risk of recurrence in prostate cancer patients

The tumour micro-environment (TME) plays a crucial role in the onset and progression of prostate cancer (PCa). Here we studied the potential of a selected panel of TME-markers to predict clinical recurrence (CLR) in PCa. Patient cohorts were matched for the presence or absence of CLR 5 years post-prostatectomy. Tissue micro-arrays (TMA) were composed with both prostate non-tumour (PNT) and PCa tissue and subsequently processed for immunohistochemistry (IHC). The IHC panel included markers for cancer activated fibroblasts (CAFs), blood vessels and steroid hormone receptors ((SHR): androgen receptor (AR), progesterone receptor (PR) and estrogen receptor (ER)). Stained slides were digitalised, selectively annotated and analysed for percentage of marker expression with standardized and validated image analysis algorithms. A univariable analysis identified several TME markers with significant impact on CR: expression of CD31 (vascular marker) in PNT stroma, expression of alpha smooth muscle actin (αSMA) in PCa stroma, and PR expression ratio between PCa stroma and PNT stroma. A multivariable model, which included CD31 expression (vascular marker) in PNT stroma and PR expression ratio between PCa stroma and PNT stroma, could significantly stratify patients for CLR, with the identification of a low risk and high-risk subgroup. If validated and confirmed in an independent prospective series, this subgroup might have clinical potential for PCa patient stratification.
Effect of storage, temperature, and extraction kit on the phylogenetic composition detected in the human milk microbiota

Human milk is considered the optimum feeding regime for newborns and is a source of bacteria for the developing infant gastrointestinal tract. However, as with all low biomass samples, standardization across variabilities such as sample collection, storage, and extraction methods is needed to eliminate discrepancies in microbial composition across studies. The aim of this study was to investigate how different storage methods, temperatures, preservatives, and extraction kits influence the human milk microbiome, compared to fresh samples. Breast milk samples were processed via six different methods: fresh (Method 1), frozen at −80°C (Method 2), treated with RNAlater and stored at 4°C or −80°C (Methods 3 and 4), and treated with Milk Preservation Solution at room temperature (Methods 5 and 6). Methods 1‐5 were extracted using PowerFoodTM Microbial DNA Isolation kit (Mobio), and Method 6 was extracted using Milk DNA Preservation and Isolation kit (Norgen BioTek). At genus level, the most abundant genera were shared across Methods 1‐5. Samples frozen at −80°C had fewest significant changes while samples treated and extracted using Milk Preservation and Isolation kit had the most significant changes when compared to fresh samples. Diversity analysis indicated that variation in microbiota composition was related to the method and extraction kit used. This study highlighted that, when extraction from fresh milk samples is not an option, freezing at −80°C is the next best option to preserve the integrity of the milk microbiome. Furthermore, our results demonstrate that choice of extraction kit had a profound impact on the microbiota populations detected in milk.
Exercise Training for Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Pulmonary hypertension (PH) is a chronic disease with a notable health burden; regular exercise may improve specific health outcome measures. Objective: The objective of this meta-analysis was to estimate the effectiveness of exercise training for PH patients. Data sources: PubMed, CINAHL, SportDiscuss and Google Scholar databases and reference lists of included studies were searched. Study selection: The selection criteria were randomized controlled trials (RCTs) employing an exercise training intervention. Data were extracted from the entered studies for analysis. The primary outcomes were peak oxygen uptake (VO2peak), anaerobic threshold (AT), 6-minute walk distance (6-MWD), and quality of life (QoL) measures (physical component score and mental component score). The analysis included 9 articles with a total of 302 participants: intervention (n = 154), and control (n = 148). Results: In the pooled analysis, improvements were seen in: VO2peak, mean difference (MD) 2.79 ml/kg/min (95% CI 2.00 to 3.59, p < 0.00001); AT, MD 107.83 ml/min (95% CI 39.64 to 176.00, p = 0.002); and 6-MWD, MD 46.67 meters (95% CI 32.39 to 60.96, p < 0.00001). Differences were found in the SF-36 physical component score MD 3.57 (95% CI 2.04 to 5.10, p < 0.00001) and the SF-36 mental component score MD 3.92 (95% CI 1.92 to 5.91, p = 0.001). Conclusion: This meta-analysis demonstrates exercise training has a beneficial effect on fitness, walking performance, and self-reported QoL in PH patients.
Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis

Background A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. Methods This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. Results Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1–11208.9] vs 626.0 [374.0–2382.2]; p = 0.004); week 3 (3893.1 [1388.2–6694.0] vs 1184.4 [461.8–2447.8]; p = 0.003); and week 4 (2736.3 [1202.1–8514.1] vs 1129.1 [542.5–2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02–23.05] vs 1.57 [0.64–2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. Conclusions Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.
A Novel Enzyme Biosensor Specific for Formaldehyde Based on pH‐Sensitive Field Effect Transistors

An enzyme biosensor specific for formaldehyde has been developed using pH-sensitive field effect transistors (FET) as a transducer and alcohol oxidase (AOX) from Hansenula polymorpha as a sensitive element. The steady-state response time of the developed biosensor was 10–60 s. The linear dynamic range (in semi-logarithmic scale) of the sensor output signal corresponded to 10–300 mmol dm−3 formaldehyde concentration. The operational stability of the biosensor was not less than 7 h and the relative standard deviation approximately 1–3%. When stored at +4°C, the response was stable for more than 30 days. The biosensor demonstrated high specificity to formaldehyde with no potentiometric response to primary alcohols. The influence of buffer concentration and enzyme concentration in the biomembrane on the sensor signal was investigated. The specific biosensor could also be successfully used for highly selective, quantitative estimation of mercury ion in an aqueous solution. © 1997 SCI.
Real-life impact of clinical prediction rules for venous thromboembolism in primary care: a cross-sectional cohort study

Objective Clinical prediction rules (CPRs) followed by D-dimer testing were shown to safely rule out venous thromboembolism (VTE) in about half of all suspected patients in controlled and experienced study settings. Yet, its real-life impact in primary care is unknown. The aim of this study was to determine the real-life impact of CPRs for suspected VTE in primary care. Design Cross-sectional cohort study. Setting Primary care in the Netherlands. Participants Patients with suspected deep venous thrombosis (n=993) and suspected pulmonary embolism (n=484). Interventions General practitioners received an educational instruction on how to use CPRs in suspected VTE. We did not rectify incorrect application of the CPR in order to mimic daily clinical care. Main outcome measures Primary outcomes were the diagnostic failure rate, defined as the 3-month incidence of VTE in the non-referred group, and the efficiency, defined as the proportion of non-referred patients in the total study population. Secondary outcomes were determinants for and consequences of incorrect application of the CPRs. Results In 267 of the included 1477 patients, VTE was confirmed. When CPRs were correctly applied, the failure rate was 1.51% (95% CI 0.77 to 2.86), and the efficiency was 58.1% (95% CI 55.2 to 61.0). However, the CPRs were incorrectly applied in 339 patients, which resulted in an increased failure rate of 3.31% (95% CI 1.07 to 8.76) and a decreased efficiency of 35.7% (95% CI 30.6 to 41.1). The presence of concurrent heart failure increased the likelihood of incorrect application (adjusted OR 3.26; 95% CI 1.47 to 7.21). Conclusions Correct application of CPRs for VTE in primary care is associated with an acceptable low failure rate at a high efficiency. Importantly, in nearly a quarter of patients, the CPRs were incorrectly applied that resulted in a higher failure rate and a considerably lower efficiency.
Preparation and evaluation of conjugate nanogels of glycyl-prednisolone with natural anionic polysaccharides as anti-arthritic delivery systems

Abstract Although prednisolone (PD) is used as an anti-arthritis drug due to its rapid and strong anti-inflammatory potential, its frequent and large dosing often brings about adverse effects. Therefore, targeting therapy has attracted increasing attention to overcome such adverse effects. In the present study, nanogels (NGs) composed of macromolecule–PD conjugates were developed as a novel targeting delivery system, and their anti-inflammatory potential was examined. Conjugates were prepared by carbodiimide coupling between glycyl-prednisolone (GP) and the natural anionic polysaccharides, alginic acid (AL) and hyaluronic acid (HA). NGs were produced by the evaporation of organic solvent from the conjugate solution. The obtained NGs, named AL-GP-NG and HA-GP-NG, respectively, were examined for particle characteristics, in vitro release, pharmacokinetics, and in vivo efficacy. Both NGs were several hundred nanometers in size, had negative zeta potentials, and several % (w/w) drug contents. They released PD gradually at pH 7.4 and 6. They exhibited fairly good retention in the systemic circulation. In the efficacy examination using rats with adjuvant-induced arthritis, both NGs showed the stronger and more prolonged suppression of paw inflammation than PD alone. These suggested that the present NGs should be possibly useful as anti-arthritis targeting therapeutic systems.
Attitude towards and experience with clozapine of patients and their caregivers after three months of starting of clozapine

Abstract Aim To evaluate the patients' perceptions of clozapine and that of their family caregivers about the positive and negative effects of clozapine. Methodology 52 patients and their family caregivers were assessed for their perception of the positive and negative effects of clozapine by using a self-designed questionnaire. Results About half (53.8%) of the patients were not distressed of frequent blood testing. At least two-thirds of the patients acknowledged a reduction in psychopathology, achieving clinical stability, improvement in the behavior of others towards them, improvement in their behavior towards others, improvement in regularity in medication intake, agreed that their clinical state will worsen if clozapine is stopped, and reported overall satisfaction/happiness with the intake of clozapine. In general, caregivers also reported similar perceptions. In terms of caregiver outcomes, about two-third to three-fourth of the caregivers reported a reduction in caregiving needs, personal caregiver distress and tension, caregiver burden and time spent in caregiving. About half of the caregivers reported a reduction in the cost of treatment, since the starting of clozapine. Conclusions To conclude, the present study suggests that a significant proportion of patients receiving clozapine for three months and their relatives report positive perception and experience with the molecule.
“Starting that Conversation Is Even Harder than Having It”: Female Patients’ Perceptions of Physicians’ Communication Competence in Communication about Sexual Behavior

Female college students demonstrate a persistent lack of knowledge about safe sexual practices and engage in sexual behavior that puts them at risk for sexually transmitted infections and unplanned pregnancy. Physicians have an opportunity to provide accurate and timely information about safe sexual behavior to individuals in their care. However, many young people, and in particular young women, are reticent to talk to their physicians about sexual behavior because they typically consider the information to be private. Exacerbating this issue is the fact that many physicians are also uncomfortable discussing sexual topics with their patients. In this study, Communication Privacy Management (CPM) theory is used to investigate the criteria that female college students employ to negotiate the disclosure and concealment of information about sexual behavior in communication with physicians. Qualitative analysis of semi-structured interviews with female college students was used to explain their perceptions of disclosure of sexual behaviors to their physician. Specifically, the participants’ perceptions of physicians’ communication competence informed privacy management rules. These findings have the potential to improve communication interventions for both female college students and healthcare professionals.
Food security and livelihoods of post-resettlement households around Kanha National Park

Globally, conservation efforts have moved millions of people out of protected areas since the 1970s, yet quantitative studies on post-resettlement well-being remain a challenge due to poor documentation. Since 2008, the Indian forest department records demographic and financial details at the household level under standardized guidelines for resettlement. Here, we examine the food security of approximately 600 households’ post-resettlement from Kanha National Park (KNP) in central India between 2009 and 2014. We compare food security of resettled households with host community households with a total of 3519 household surveys, conducted over three seasons within one year. We measure food security using food consumption scores (FCSs), coping strategies index (CSI) and household hunger scale (HHS). Food insecurity is widespread in the landscape, with over 80% of households reporting poor or borderline FCSs year-round. Additionally, we recorded food insecurity increases in monsoon for all households regardless of resettlement status. Results indicate that resettled households are comparable to their host community neighbors in FCS and all households use mild coping strategies to combat food insecurity. While widespread, food insecurity in the KNP landscape is not acute with very few (<10) reports of severe hunger (as measured by the HHS). Almost all foods are market bought (>90%) and sometimes supplemented by gathering locally prevalent greens or from kitchen gardens (forest dependency for food was negligible). Accruing assets and diversifying incomes from non-labor avenues would alleviate food insecurity for all households. The patterns of market dependence and food security associated with diversified stable incomes around protected areas is in contrast with many studies but is likely to occur in similar human-dominated landscapes.