Miracle-dz/UniFAR-FTUs huggingface dataset:
Does Q‐MIX pretreatment improve the dentin bond durability of a two‐step self‐etch adhesive?

This study aims to analyze and assess the effects of three particular dentin pretreatment solutions on the bond durability of a two‐step self‐etch adhesive (Optibond XTR) applied to dentin after ageing for 2 years. Thirty‐five third molars which were extracted (n = 5 for μTBS, n = 2 for nanoleakage) were divided into five groups: Group 1:Control (no pretreatment), Group 2:17% EDTA, Group 3:2% CHX, Group 4:17% EDTA plus 2% CHX, Group 5: Q‐Mix. After the pretreatments of dentin, the dentin adhesive was applied as per the guidelines provided by the manufacturer. Half of the specimens were subjected to μTBS tests for 24 hr, while the remaining half were subjected to the tests after being kept for 2 years in water storage. Also, nanoleakage was evaluated with FE‐SEM by examining silver nitrate deposits. The data obtained were evaluated using a two‐way analysis of variance and Tukey Post Hoc test. The dentin pretreatments did not affect the 24 hr and 2 years μTBS values for OptiBond XTR. At 24 hr, the EDTA + CHX group (50.3 ± 4.9) showed that the highest μTBS value was obtained. Water ageing significantly reduced the μTBS results and after 2 years the highest μTBS value was obtained from the Q‐Mix group (37.7 ± 5.2). Different dentin pretreatments do not alter the 24‐hr μTBS and were not able to preserve the bond strength after 2 years of ageing. Q‐Mix was able to slow down the regression in the strength of the dentin bond as well as nanoleakage over time.
Adapting a Low-threshold Buprenorphine Program for Vulnerable Populations During the COVID-19 Pandemic

Objectives: To examine patient characteristics and outcomes among opioid use disorder patients enrolled in low-threshold buprenorphine treatment during the COVID-19 pandemic. Methods: This paper describes the adaptation of the Project Connections (PC) program, a low-threshold buprenorphine program in Baltimore, in response to the COVID-19 pandemic. This paper examines patient characteristics and initial outcomes of patients served during a rapid protocol shift to telehealth that allowed buprenorphine initiation without an in-person encounter following a state-mandated stay-at-home order. Patient characteristics were compared to a subsample of patients enrolled in the program before the COVID-19 pandemic. Results: In March 2020, there was a sharp increase in new enrollments to the PC program. A total of 143 patients completed an intake assessment between March and May 2020 and 140 began treatment with buprenorphine/naloxone. Those who completed an intake assessment were primarily male (68.5%), Black (83.2%), had a mean age of 43.2 years (SD = 11.7), and reported a mean of 17.0 years of opioid use (SD = 12.9). The majority of patients were unemployed (72.7%) and reported previous criminal justice involvement (69.2%). Of those who completed an intake assessment, 96.5% returned for a second visit. Among those for whom 30-day retention data was available (n = 113), 63.7% were engaged for 30 days or longer. Conclusions: The PC program illustrates that offering on-demand, flexible treatment is an opportunity to increase opioid use disorder treatment access, even during a public health emergency that disrupted access to services. Relaxation of buprenorphine telehealth regulations allowed for flexibility in treatment and benefits vulnerable populations.
Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure

Background: Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)—a novel activator of cardiac myosin—improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure). Methods: Patients (n=448) were randomized 1:1:1 to placebo, 25 mg of OM BID, or to pharmacokinetically guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score, Physical Limitation Scale, and Clinical Summary Score. Results: Mean change in score from baseline to 20 weeks for the Total Symptom Score was 5.0 (95% CI, 1.8–8.1) for placebo, 6.6 (95% CI, 3.4–9.8) for OM 25 mg (P=0.32 versus placebo), and 9.9 (95% CI, 6.7–13.0) for OM-PK (P=0.03 versus placebo); for the Physical Limitation Scale, it was 3.1 for placebo (95% CI, −0.3 to 6.6), 6.0 (95% CI, 3.1–8.9) for OM 25 mg (P=0.12), and 4.3 (95% CI, 0.7–7.9) for OM-PK (P=0.42); for the Clinical Summary Score, it was 4.1 (95% CI, 1.4–6.9) for placebo, 6.3 (95% CI, 3.6–9.0) for OM 25 mg (P=0.19), and 7.0 (95% CI, 4.1–10.0) for OM-PK (P=0.14). Differences between OM and placebo were greater in patients who were more symptomatic at baseline. Conclusions: HRQL as measured by the Total Symptom Score improved in patients with heart failure with reduced ejection fraction assigned to the OM-PK group relative to placebo. Ongoing trials are prospectively testing whether OM improves symptoms and HRQL in heart failure with reduced ejection fraction. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT01786512.
Managing enzyme promiscuity in plant specialized metabolism: A lesson from flavonoid biosynthesis

Specificities of enzymes involved in plant specialized metabolism, including flavonoid biosynthesis, are generally promiscuous. This enzyme promiscuity has served as an evolutionary basis for new enzyme functions and metabolic pathways in land plants adapting to environmental challenges. This phenomenon may lead, however, to inefficiency in specialized metabolism and adversely affect metabolite‐mediated plant survival. How plants manage enzyme promiscuity for efficient specialized metabolism is, thus, an open question. Recent studies of flavonoid biosynthesis addressing this issue have revealed a conserved strategy, namely, a homolog of chalcone isomerase with no catalytic activity binds to chalcone synthase, a key flavonoid pathway enzyme, to narrow (or rectify) the enzyme's highly promiscuous product specificity. Reducing promiscuity via specific protein–protein interactions among metabolic enzymes and proteins may be a solution adopted by land plants to achieve efficient operation of specialized metabolism, while the intrinsic promiscuity of enzymes has likely been retained incidentally.
A case of inferior frontal gyrus infarction manifesting Gerstmann syndrome

ABSTRACT A 48-year-old female suffered from cerebral infarction involving the left inferior frontal gyrus. This was due to ischemic complications of endovascular treatment for subarachnoid hemorrhage. She exhibited severe acalculia, agraphia, finger agnosia, and right-left disorientation (the four features of Gerstmann syndrome), but aphasia was scarcely noticeable. Single-photon emission tomography revealed hypoperfusion in the left inferior frontal area and also in the left parietal area. It is possible that Gerstmann syndrome was caused in the present case by disruption of the association fiber connecting the inferior frontal area with the inferior parietal area.
Music therapy for stress reduction: a systematic review and meta-analysis

ABSTRACT Music therapy is increasingly being used as an intervention for stress reduction in both medical and mental healthcare settings. Music therapy is characterized by personally tailored music interventions initiated by a trained and qualified music therapist, which distinguishes music therapy from other music interventions, such as ‘music medicine’, which concerns mainly music listening interventions offered by healthcare professionals. To summarize the growing body of empirical research on music therapy, a multilevel meta-analysis, containing 47 studies, 76 effect sizes and 2.747 participants, was performed to assess the strength of the effects of music therapy on both physiological and psychological stress-related outcomes, and to test potential moderators of the intervention effects. Results showed that music therapy showed an overall medium-to-large effect on stress-related outcomes (d = .723, [.51–.94]). Larger effects were found for clinical controlled trials (CCT) compared to randomized controlled trials (RCT), waiting list controls instead of care as usual (CAU) or other stress-reducing interventions, and for studies conducted in Non-Western countries compared to Western countries. Implications for both music therapy and future research are discussed.
Methylprednisolone pulse treatment improves ProSP‐C trafficking in twins with SFTPC mutation: An isoform story?

Mutations in the gene encoding surfactant protein C (SP‐C) cause interstitial lung disease (ILD), and glucocorticosteroid (GC) treatment is the most recognized therapy in children. We aimed to decipher the mechanisms behind successful GC treatment in twins carrying a BRICHOS c.566G > A (p.Cys189Tyr) mutation in the SP‐C gene (SFTPC).
Reduction in nickel content of the surface oxide layer on Ni-Ti alloy by electrolytic treatment.

PURPOSE Ni-Ti alloy has been increasingly applied to dental and medical devices, however, it contains nickel, which is known to have adverse effects on the human body. The purpose of this study was to form a nickel-free surface oxide layer on Ni-Ti alloy by electrolytic treatment for better biocompatibility. METHODS Ni-49.15Ti (mol%) alloy was used, and the electrolytic treatment was performed in the electrolytes under 50 V for 30 minutes. The electrolytes were composed of lactic acid, water, and glycerol with different compositions. Surface analysis and characterization of Ni-Ti alloy were carried out by means of X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). RESULTS Results indicated that the outmost surface oxide layer was nickel-free when using an electrolyte comprising 7.1% lactic acid, 57.2% water, and 35.7% glycerol by volume. The composition of this nickel-free surface oxide layer was determined as TiO1.92(OH)1.35 ∙ 0.43H2O by XPS, similar to that of unalloyed titanium. The thickness of this nickel-free layer was estimated at 6.4 nm by AES. CONCLUSION The nickel-free surface oxide layer produced on Ni-Ti alloy is considered to improve the biocompatibility of medical and dental devices having shape memory effect and/or super-elasticity.
cDNA-Derived RNA Phage Assembly Reveals Critical Residues in the Maturation Protein of the Pseudomonas aeruginosa Leviphage PP7

The biological significance of RNA phages has been largely ignored, ironically, because few studies have focused on RNA phages. As an initial attempt to properly represent RNA phages in the phageome, we previously created, by using reverse-transcribed cDNA, a reverse genetic system for the small RNA phage PP7, which infects the opportunistic human pathogen Pseudomonas aeruginosa. ABSTRACT PP7 is a leviphage, with a single-stranded RNA genome, that infects Pseudomonas aeruginosa PAO1. A reverse genetic system for PP7 was previously created by using reverse-transcribed cDNA (PP7O) from a virion-derived RNA genome. Here, we have found that the PP7O cDNA contained 20 nucleotide differences from the PP7 genome sequence deposited in the database. We created another reverse genetic system exploiting chemically synthesized cDNA (PP7S) based on the database sequence. Unlike PP7O, which yielded infectious PP7 virions, PP7S-derived particles were incapable of plaque formation on PAO1 cells, which was restored in the PAO1 cells expressing the maturation protein (MP) from PP7O. Using this reverse genetic system, we revealed two amino acid residues involved in the known roles of MP (i.e., adsorption and genome replication), fortuitously providing a lesson that the viral RNA genome sequencing needs functional verification, possibly by a reverse genetic system. IMPORTANCE The biological significance of RNA phages has been largely ignored, ironically, because few studies have focused on RNA phages. As an initial attempt to properly represent RNA phages in the phageome, we previously created, by using reverse-transcribed cDNA, a reverse genetic system for the small RNA phage PP7, which infects the opportunistic human pathogen Pseudomonas aeruginosa. We report another system by using chemically synthesized cDNA based on the database genome that has 20 nucleotide differences from the previous cDNA. Investigation of those cDNA-derived phage virions revealed that two amino acids of the maturation protein are crucial for the normal phage lifecycle at different steps. Our study provides insight into the molecular basis for the RNA phage lifecycle and a lesson that the RNA genome sequencing needs to be carefully validated by cDNA-based phage assembly systems.
Hydrogen sulfide mediates defense response in safflower by regulating secondary metabolism, oxidative defense and elemental uptake under drought.

Hydrogen sulfide (H2 S) is a newly recognized molecule mediating plant defense responses under drought. The role of exogenous H2 S in regulating plant responses under drought has been reported in a few plant species including spinach, wheat, Arabidopsis, soybean, and citrus plants. However, no report is available on the outcome of exogenous H2 S on drought response in safflower plants. Therefore, the present study was planned to get insight into H2 S-mediated regulation of growth, secondary metabolism, oxidative defense and uptake of minerals in two safflower cultivars (Safflower-16427 and Safflower-16493). Plants were exposed to two NaHS (0.5 and 1.0 mM) and two drought levels (70 and 50% field capacity (FC)). We found a notable depression in growth, yield, chlorophyll, and potassium (K+ ) uptake under drought. The decline was more significant in plants facing 50% FC. The oxidative injury in plants was higher under severe drought and lead to the decline in chlorophyll, plant biomass and yield production. Drought induced a noticeable accretion in the accumulation of total soluble sugars, proline, ascorbic acid, anthocyanins, and secondary metabolites that protect plants against oxidative damages caused by drought. The activities of antioxidant enzymes increased substantially in safflower cultivars under drought. Besides, plants pretreated with NaHS (0.5 mM) subsided the oxidative damage by increasing the accumulation of secondary metabolites and strengthening the antioxidant capacity under drought. Further, drought plants suffered significant disturbances in ions homeostasis that was circumvented by exogenous H2 S. The interactive effect of drought and H2 S did not display a significant difference between the cultivars. This article is protected by copyright. All rights reserved.
Clinical Outcomes After Total Pancreatectomy

Objective: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. Background: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. Methods: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018–June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60). Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. Results: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9–18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18–12.16, P = 0.026), age (OR 1.07, 95% CI 1.01–1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64–53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56–5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25–9.90, P = 0.017) were associated with major complications. Conclusion: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.
Bilateral severe microphthalmia in a neonate with trisomy 8 mosaicism: A new finding

Mosaic Trisomy 8 is a rare chromosomal abnormality estimated to occur one in 30,000 newborns. The phenotype is highly variable and the severity does not appear to be correlated with the proportion of cells that contain the additional chromosome. Ocular involvement in Trisomy 8 mosaicism has previously been described to include corneal opacities, retinal dystrophy, coloboma, and unilateral microphthalmia. We report a case of severe bilateral microphthalmia in a neonate with Trisomy 8 mosaicism, a previously unrecognized ophthalmic manifestation.
Single‐cell transcriptome analyses reveal heterogeneity in suspension cultures and clonal markers of CHO‐K1 cells

Cell‐to‐cell variability in cell populations arises from a combination of intrinsic factors and extrinsic factors related to the milieu. However, the heterogeneity of high cell density suspension cultures for therapeutic protein production remains unknown. Here, we illustrate the increasing heterogeneity in the cellular transcriptome of serum‐free adapted CHO K1 cells during high cell density suspension culture over time without concomitant changes in the genomic sequence. Cell cycle‐dependent subpopulations and cell clusters, which typically appear in other single‐cell transcriptome analyses, were not found in these suspension cultures. Our results indicate that cell division changes the intracellular microenvironment and leads to cell cycle‐dependent heterogeneity. Whole mitochondrial single‐cell genome sequencing showed cell‐to‐cell mitochondrial genome variation and heteroplasmy within cells. The mitochondrial genome sequencing method developed here is potentially useful for the validation of cell clonality. The culture time‐dependent increase in cellular heterogeneity observed in this study did not show any attenuation in this increasing heterogeneity. Future advances in bioengineering such as culture upscaling, prolonged culturing, and complex culture systems will be confronted with the need to assess and control cellular heterogeneity, and the method described here may prove useful for this purpose.
PRIMPOL ready, set, reprime!

Abstract DNA replication forks are constantly challenged by DNA lesions induced by endogenous and exogenous sources. DNA damage tolerance mechanisms ensure that DNA replication continues with minimal effects on replication fork elongation either by using specialized DNA polymerases, which have the ability to replicate through the damaged template, or by skipping the damaged DNA, leaving it to be repaired after replication. These mechanisms are evolutionarily conserved in bacteria, yeast, and higher eukaryotes, and are paramount to ensure timely and faithful duplication of the genome. The Primase and DNA-directed Polymerase (PRIMPOL) is a recently discovered enzyme that possesses both primase and polymerase activities. PRIMPOL is emerging as a key player in DNA damage tolerance, particularly in vertebrate and human cells. Here, we review our current understanding of the function of PRIMPOL in DNA damage tolerance by focusing on the structural aspects that define its dual enzymatic activity, as well as on the mechanisms that control its chromatin recruitment and expression levels. We also focus on the latest findings on the mitochondrial and nuclear functions of PRIMPOL and on the impact of loss of these functions on genome stability and cell survival. Defining the function of PRIMPOL in DNA damage tolerance is becoming increasingly important in the context of human disease. In particular, we discuss recent evidence pointing at the PRIMPOL pathway as a novel molecular target to improve cancer cell response to DNA-damaging chemotherapy and as a predictive parameter to stratify patients in personalized cancer therapy. Graphical Abstract
Regulating the reactivity of black phosphorus via protective chemistry

Black phosphorus is stabilized by ionic/hydrophobic protection, whereas its reactivity is resumed by chelator deprotection. Rationally regulating the reactivity of molecules or functional groups is common in organic chemistry, both in laboratory and industry synthesis. This concept can be applied to inorganic nanomaterials, particularly two-dimensional black phosphorus (BP) nanosheets. The high reactivity of few-layer (even monolayer) BP is expected to be “shut down” when not required and to be resumed upon application. Here, we demonstrate a protective chemistry–based methodology for regulating BP reactivity. The protective step initiates from binding Al3+ with lone pair electrons from P to decrease the electron density on the BP surface, and ends with an oxygen/water-resistant layer through the self-assembly of hydrophobic 1,2-benzenedithiol (BDT) on BP/Al3+. This protective step yields a stabilized BP with low reactivity. Deprotection of the obtained BP/Al3+/BDT is achieved by chelator treatment, which removes Al3+ and BDT from the BP surface. The deprotective process recovers the electron density of BP and thus restores the reactivity of BP.
Preparation of Gastro-retentive Tablets Employing Controlled Superporous Networks for Improved Drug Bioavailability

The development of an oral formulation that ensures increased bioavailability of drugs is a great challenge for pharmaceutical scientists. Among many oral formulation systems, a drug delivery system employing superporous networks was developed to provide a prolonged gastro-retention time as well as improved bioavailability of drugs with a narrow absorption window in the gastrointestinal tract. Superporous networks (SPNs) were prepared from chitosan by crosslinking with glyoxal and poly(vinyl alcohol) (PVA). The SPNs showed less porosity and decreased water uptake with an increase in the crosslinking density and content of PVA. Gastro-retentive tablets (GRTs) were formulated using hydroxypropyl methylcellulose (HPMC, a hydrophilic polymer) and the prepared SPNs. Ascorbic acid (AA), which is mainly absorbed in the proximal part of the small intestine, was selected as a model drug. The formulated GRTs exhibited no floating lag time and stayed afloat until the end of the dissolution test. The in vitro drug release from the GRTs decreased with a decrease in the water uptake of the SPNs. The profile of drug release from the GRTs corresponded to the first-order and Higuchi drug-release models. Overall, floating tablets composed of the SPNs and HPMC have potential as a favorable platform to ensure sustained release and improved bioavailability of drugs that are absorbed in the proximal part of the small intestine.