Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Chemical Binding Primer to Improve Dentin Bonding Durability

The dentin collagen matrix that is not completely enveloped by resin adhesive is vulnerable to degradation by intrinsic collagenases during the etch-and-rinse process, which contributes to the deterioration of the bonding interface. Current commercial adhesives have no functional components that can form covalent bonds to the dentin collagen matrix. In this study, a photocurable aldehyde, 4-formylphenyl acrylate (FA), was synthesized and for the first time applied as a primer in adhesive dentistry to covalently bind to collagen. Experimental groups with different concentrations of FA (1%, 3%, 5%, 7%, 9%) were prepared as primers. The cytotoxicity was evaluated by live/dead-cell staining and thiazolyl blue tetrazolium bromide assay. The interaction of FA with collagen was examined by attenuated total reflection Fourier transform infrared spectroscopy, hydroxyproline release under the degradation of type I collagenase, and thermogravimetric analysis. An optimal group was selected based on the degree of conversion of 2 universal adhesives and further divided depending on the treatment time (20 s, 30 s, 1 min, 2 min). The bonding performances were evaluated by microtensile strength before and after aging. Finally, the bonding interface was observed under confocal laser scanning microscopy and scanning electron microscope. The results indicated that FA demonstrated good biocompatibility, dentin modification capability, and infiltration. It not only effectively cross-linked dentin collagen to improve its stability against enzymatic hydrolysis and modify the adhesive interface but also potentially acted as a diluting monomer to induce deep penetration of adhesive resin monomers into the dentin. The bonding strength after aging was improved without jeopardizing the degree of conversion of 2 commercial adhesives. Such prominent advantages of using FA to improve the bonding performance promotes its further application in adhesive dentistry.
Pilot study on the impact of a carbohydrate loading drink on postprandial glycemic responses and gastric emptying in adults with prediabetes and type 2 diabetes mellitus

Abstract Background Preoperative carbohydrate (CHO) loading improves patient outcomes but is not extensively studied in individuals with diabetes mellitus (DM), resulting in limited professional recommendations. This study examined postprandial glycemic responses and gastric emptying rates following consumption of a CHO drink in adults with and without DM. Methods A single‐arm, nonrandomized pilot trial was conducted in adults without DM (non‐DM) (47.5 ± 2.5 years), with pre‐DM (55.8 ± 3.0 years), and with type 2 DM (56.2 ± 2.5 years). Following an overnight fast, participants consumed a 50 g CHO drink followed by 1.5 g liquid paracetamol. Venous blood samples were collected at baseline (ie, t = 0 min) and 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min for plasma glucose and serum insulin and paracetamol concentrations to assess gastric emptying. Results Participants with DM were older and had a higher body mass index than non‐DM participants (31.2 ± 0.9 vs 28.2 ± 0.9). Fasting glucose and hemoglobin A1c levels differed significantly across groups (non‐DM: 95.4 ± 3.6 mg/dl and 5.2% ± 0.1%; pre‐DM: 111.6 ± 3.6 mg/dl and 5.8% ± 0.1%; DM: 167.4 ± 3.6 mg/dl and 7.2% ± 0.1%). Compared with the non‐DM group, DM had increased glucose responses at 30–180 min. Glucose returned to baseline at 150 min in the non‐DM and pre‐DM groups compared with 210 min in the DM group. Paracetamol concentrations were not significantly different between the non‐DM and DM groups. Conclusion Blood glucose returned to baseline within ~2.5 h in non‐DM and pre‐DM groups and ~3.5 h in participants with DM following ingestion of a CHO drink. No consistent differences in gastric emptying rates were observed between participants with and without DM.
Angiogenin and MMP-2 as potential biomarkers in the differential diagnosis of gestational trophoblastic diseases

Abstract Background: Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process. Material and methods: We determined ANG and MMP-2 in the placental tissues of 26 patients who had a benign mole (BM), 12 patients with gestational trophoblast neoplasia (GTN) (1 invasive hydatidiform mole, 10 choriocarcinomas, and 1 placental-site trophoblastic tumor), and 28 normal chorionic villi (NCV) subjects using immunohistochemistry staining. We obtained the serum samples from 20 patients with GTDs and 20 early pregnant women and evaluated them by the enzyme linked immunosorbent assay. Results: ANG expression in GTN (66.7%) and BM (100%) samples were both significantly higher (strong/intermediate staining) than in NCV (60.7%) samples (P < .001). Similarly, the immunoreactivities of MMP-2 in the GTN (66.7%) and BM (80.8%) samples were significantly elevated compared to that of the NCV (57.1%) samples (P < .001). The levels of ANG and MMP-2 in the maternal serum of the GTN group were both significantly higher than those of the control group (P < .001). ANG and MMP-2 expressions were associated with gestation age, clinical stage, and FIGO stage. A positive correlation between ANG and MMP-2 expression was observed (rs = 0.725; P < .01). Conclusion: ANG and MMP-2 levels were significantly elevated in the placental tissues and maternal serum from patients with GTDs. Further studies with more patients may clarify the vascular abnormalities in GTDs and determine potential biomarkers in the differential diagnosis of GTDs.
Adaptation and norming of the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS) for three language groups in South Africa

Abstract Objectives: To adapt and translate the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS); to generate preliminary normative data for three language groups in South Africa (SA); to assess the convergent validity of the ECAS in SA samples. Methods: The ECAS was linguistically and culturally adapted for Afrikaans-, isiXhosa-, and English-speaking SA adults (n = 108, 100, and 53, respectively). Each language group was stratified by age and educational level. Cutoff scores for cognitive impairment were set at the group mean minus two standard deviations (SDs). A pilot sample of ALS patients and controls (n = 21 each) were administered the ECAS and an extensive neuropsychological evaluation (NPE) and the Montreal Cognitive Assessment (MoCA) to assess convergent validity. Results: Across the three language groups, the total ECAS cutoff scores ranged from 68 to 97. The ECAS score correlated significantly positively with educational level (p < 0.001) and negatively with age (p < 0.005). The restricted letter fluency task demonstrated a floor effect, particularly in Afrikaans-speakers. The mean total ECAS score (±SD) was similar in ALS patients (103.52 ± 11.90) and controls (100.67 ± 20.49; p = 0.58). Three (14.3%) ALS patients scored below the cutoff for cognitive impairment. Correlations between individual ECAS subtests and analogous NPE tests ranged from weak to moderate. The MoCA score was significantly positively correlated with the ECAS total score (r = 0.59; p = < 0.001). Conclusions: The adapted ECAS and associated normative data will aid cognitive screening of African ALS patients. Larger participant numbers are needed to assess the validity of the adapted instrument.
Clinical signs and symptoms associated with acute HIV infection from an intensely monitored cohort on 2 continents

Supplemental Digital Content is available in the text Abstract Define the clinical presentation of acute human immunodeficiency virus infection (AHI) among men and women from 2 continents to create a clinical scoring algorithm. Comparison of incident sign and symptom between those with and without AHI. At-risk human immunodeficiency virus (HIV) negative men and women in Thailand, Kenya, Tanzania, and Uganda underwent twice-weekly testing for HIV. Newly diagnosed participants were evaluated twice weekly for 21 days after infection. Of the 3345 participants enrolled, 56 African females and 36 biological males from Thailand were diagnosed with AHI. Four hundred fifty-two of their encounters were compared to 18,281 HIV negative encounters. Due to a high degree of heterogeneity among incident symptoms, 2 unique subgroups based upon geography and sex were created. Among Thai males, the signs and symptoms with the greatest odds ratio (OR) between AHI and uninfected participants were nausea (OR 16.0, 95% confidence interval [CI] 3.9–60.2, P < .001) and lymphatic abnormalities (OR 11.8, 95% CI 4.2–49.0, P < .001); and among African females were pain behind the eyes (OR 44.4, 95% CI 12.0–158.0, P < .0001) and fatigue (OR 22.7, 95% CI 11.3–44.3, P < .001). The Thai male scoring algorithm had a 66% sensitivity and 84% specificity while the African female algorithm had a sensitivity of 27% and specificity of 98%. The different incident symptoms during AHI necessitated creating 2 different scoring algorithms that can guide diagnostic testing among a particular sex in the appropriate geographic setting. Further research on risk exposure, sex, and demographic specific models is warranted.
From Trait Affect and Conscientiousness to Individual Entrepreneurial Orientation: The Mediating Role of Cognitive Flexibility

Abstract This study investigates the mediating role of cognitive flexibility on the relationship between trait positive/negative affect, and conscientiousness with individual entrepreneurial orientation. A total of 508 (175 male and 333 female) undergraduate students participated in the study. Three separate mediation analyses were carried out. The results revealed that cognitive flexibility partially mediated the relationship between trait positive affect and individual entrepreneurial orientation as well as the relationship between conscientiousness and individual entrepreneurial orientation. The results also showed that cognitive flexibility fully mediated the association between trait negative affect and individual entrepreneurial orientation. Findings of this study show that interventions and individual development programs may be conducted to increase cognitive flexibility of individuals with high levels of trait negative affect, low levels of conscientiousness and low levels of trait positive affect. This might potentially strengthen their levels of individual entrepreneurial orientation.
Chronic hM4Di-DREADD-Mediated Chemogenetic Inhibition of Forebrain Excitatory Neurons in Postnatal or Juvenile Life Does Not Alter Adult Mood-Related Behavior

Abstract G-protein-coupled receptors (GPCRs) coupled to Gi signaling, in particular downstream of monoaminergic neurotransmission, are posited to play a key role during developmental epochs (postnatal and juvenile) in shaping the emergence of adult anxiodepressive behaviors and sensorimotor gating. To address the role of Gi signaling in these developmental windows, we used a CaMKIIα-tTA::TRE hM4Di bigenic mouse line to express the hM4Di-DREADD (designer receptor exclusively activated by designer drugs) in forebrain excitatory neurons and enhanced Gi signaling via chronic administration of the DREADD agonist, clozapine-N-oxide (CNO) in the postnatal window (postnatal days 2–14) or the juvenile window (postnatal days 28–40). We confirmed that the expression of the HA-tagged hM4Di-DREADD was restricted to CaMKIIα-positive neurons in the forebrain, and that the administration of CNO in postnatal or juvenile windows evoked inhibition in forebrain circuits of the hippocampus and cortex, as indicated by a decline in expression of the neuronal activity marker c-Fos. hM4Di-DREADD-mediated inhibition of CaMKIIα-positive forebrain excitatory neurons in postnatal or juvenile life did not impact the weight profile of mouse pups, and also did not influence the normal ontogeny of sensory reflexes. Further, postnatal or juvenile hM4Di-DREADD-mediated inhibition of CaMKIIα-positive forebrain excitatory neurons did not alter anxiety- or despair-like behaviors in adulthood and did not impact sensorimotor gating. Collectively, these results indicate that chemogenetic induction of Gi signaling in CaMKIIα-positive forebrain excitatory neurons in postnatal and juvenile temporal windows does not appear to impinge on the programming of anxiodepressive behaviors in adulthood.
Metabolic Side Effects of Olanzapine in Patients With Psychotic Disorders in Oman: A Retrospective Cohort Study

We evaluated the impact of olanzapine on metabolic changes in patients with psychotic disorders. This was a retrospective cohort study involving patients prescribed olanzapine and attending Sultan Qaboos University Hospital (Muscat, Oman). Patients were followed up retrospectively from March 2006 until April 2021. Cardiovascular treatment targets were evaluated as per the 2019 European Society of Cardiology guidelines. We enrolled 253 patients (mean age: 40±17 years). Olanzapine monotherapy was associated with increased body weight (+8 kg; 95% confidence interval (CI): 6–9; P < . 001), body mass index (+3 kg/m2; 95% CI: 2–4; P < .001), total cholesterol (+.4 mmol/L; 95% CI: .3–.5; P < .001), low-density lipoprotein cholesterol (LDL-C) (+.3 mmol/L; 95% CI: .1–.4; P < .001), fasting triglycerides (+.2 mmol/L; 95% CI: .1–.3; P<.001), fasting glucose (+.6 mmol/L; 95% CI: .4–.7; P< .001), HbA1c (+.3%; 95% CI: .2–.4; P < .001), systolic blood pressure (BP) (+9 mmHg; 95% CI: 6–12; P < .001) and diastolic BP (+4 mmHg; 95% CI: 2–6; P < .001) levels. Cardiovascular therapeutic goals were attained in 38% (n = 97), 61% (n = 154), 71% (n = 180), and 59% (n = 150) for LDL-C, non–high-density lipoprotein cholesterol, triglycerides, and BP, respectively. Olanzapine was associated with adverse metabolic changes. Therefore, many patients were not at their target cardiovascular treatment goals.
Developing and validating a multivariable prediction model for predicting costs of Colorectal Surgery

Hospitals are faced with a burden to predict and therefore to calculate and also to manage various cost factors in regard to the patients and their treatments. Especially the increased costs which occur if a patient suffers from an anastomotic insufficiency. This can lead to an unavoidable deficit in the final revenue of these medical centers. This study aims to determine whether machine learning (ML) algorithms can predict the cost factors based on patients with and without colon anastomosis after colorectal surgery. For the forecasting, multiple predictors will be taken into the model to provide a tool which can be helpful for hospitals to manage their costs, which can end up in operating more cost effectively. This proof of principle will lay the groundwork for an efficient ML-based prediction tool based on multicenter data from a range of international centers in the subsequent phases of the study. With a % MAPE result of 18 to 25.6 the prediction if our model showed decent results in order to forecast the costs in regard to various diagnosed factors and surgery approaches. There is an urgent need for further studies on predicting cost factors, especially for cases with and without anastomotic leakage to minimize unnecessary costs for the hospitals.
Changes to hypothalamic volume and associated subfields during gender-affirming hormone treatment in gender dysphoria

Sex steroid hormones influence hypothalamic micro- and macrostructure in humans and animal models. Neuroimaging studies have suggested that estrogen and anti-androgen treatment decreases volumes of multiple cortical and subcortical brain areas in transgender individuals, including total hypothalamus volume. Here, we aim to further explore potential effects of gender-affirming hormone treatment (GHT) in transgender individuals on hypothalamic volume by providing additional information on hypothalamic subfields. 38 transgender men (TM) and 15 transgender women (TW), with gender dysphoria (DSM-5), as well as 32 cisgender women (CW) and 21 cisgender men (CM) underwent two magnetic resonance imaging (MRI) measurements with an interval of at least four months (median interval TM= 134.5 days (interquartile range (IQR): 126-152.25); TW= 149 days (IQR: 126-178.5); CW= 147 days (IQR: 139.75-170.5); CM= 146 days (IQR: 132-247)) between both sessions. In transgender individuals GHT, consisting of estrogen and anti-androgen treatment in TW and testosterone treatment in TM, was initiated directly after the first measurement. To assess how GHT interacts with hypothalamic structures, the hypothalamus and its subunits were segmented using FreeSurfer. Subject group x time interaction effects were evaluated using repeated measures ANCOVA models. The Bonferroni method was used to correct for multiple comparisons. Significant decreases of total hypothalamic volume and associated subunits were detected in TW after estrogen and anti-androgen treatment compared to cisgender groups. Effects were found in the total hypothalamus volume (pcorr= 0.001), the left and right hypothalamus (pcorr= 0.002), the inferior tubular subunit bilaterally (right: pcorr= 0.001; left: pcorr= 0.001), the left superior tubular subunit (pcorr= 0.003) the right anterior inferior subunit (pcorr= 0.002), as well as the right anterior superior subunit (pcorr= 0.0002) of the hypothalamus. Here, we observed significant volumetric effects on the adult human hypothalamus after an interval of at least four months of estrogen and anti-androgen treatment in TW and added knowledge on associated subfields. Further studies investigating influences of sex steroid hormones on brain structure and functional connections are still needed.
Express Yourself: Quantitative Real-Time PCR Assays for Rapid Chromosomal Antimicrobial Resistance Detection in Pseudomonas aeruginosa

The rise of antimicrobial-resistant (AMR) bacteria is a global health emergency. One critical facet of tackling this epidemic is more rapid AMR diagnosis in serious multidrug-resistant pathogens like Pseudomonas aeruginosa. ABSTRACT The rise of antimicrobial-resistant (AMR) bacteria is a global health emergency. One critical facet of tackling this epidemic is more rapid AMR diagnosis in serious multidrug-resistant pathogens like Pseudomonas aeruginosa. Here, we designed and then validated two multiplex quantitative real-time PCR (qPCR) assays to simultaneously detect differential expression of the resistance-nodulation-division efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM, the AmpC β-lactamase, and the porin OprD, which are commonly associated with chromosomally encoded AMR. Next, qPCRs were tested on 15 sputa from 11 participants with P. aeruginosa respiratory infections to determine AMR profiles in vivo. We confirmed multiplex qPCR testing feasibility directly on sputa, representing a key advancement in in vivo AMR diagnosis. Notably, comparison of sputa with their derived isolates grown in Luria-Bertani broth (±2.5% NaCl) or a 5-antibiotic cocktail showed marked expression differences, illustrating the difficulty in replicating in vivo expression profiles in vitro. Cystic fibrosis sputa showed significantly reduced mexE and mexY expression compared with chronic obstructive pulmonary disease sputa, despite harboring fluoroquinolone- and aminoglycoside-resistant strains, indicating that these loci do not contribute to AMR in vivo. oprD was also significantly downregulated in cystic fibrosis sputa, even in the absence of contemporaneous carbapenem use, suggesting a common adaptive trait in chronic infections that may affect carbapenem efficacy. Sputum ampC expression was highest in participants receiving carbapenems (6.7 to 15×), some of whom were simultaneously receiving cephalosporins, the latter of which would be rendered ineffective by the upregulated ampC. Our qPCR assays provide valuable insights into the P. aeruginosa resistome, and their use on clinical specimens will permit timely treatment alterations that will improve patient outcomes and antimicrobial stewardship measures.
Efficacy and safety of nitazoxanide combined with ritonavir-boosted atazanavir for the treatment of mild to moderate COVID-19

Background: Finding effective therapeutics for COVID-19 continues to be an urgent need, especially considering use context limitations and cost of currently approved agents. The NACOVID trial investigated the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, used in combination for COVID-19. Methods: In this pilot, randomized, open label trial conducted in Nigeria, patients diagnosed with mild to moderate COVID-19 were randomly assigned to receive standard of care (SoC) or SoC plus 14-day course of nitazoxanide (1000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptoms resolution. Safety and pharmacokinetics of nitazoxanide active metabolite, tizoxanide, were also evaluated. This trial was registered with ClinicalTrials.gov (NCT04459286). Findings: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492-1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2 to 28 in the 35% of patients with detectable virus at baseline (20/57) between the two arms (aHR = 0.948, 95% CI: 0.341-2.636, p = 0.919). There was no significant difference in time from enrolment to complete symptoms resolution (aHR = 0.535, 95% CI: 0.251 -1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1546 ng/ml (95% CI: 797-2557), above its putative EC90 in 54% of patients. Tizoxanide was not detectable in saliva. Interpretation: These findings should be interpreted in the context of incomplete enrolment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial.