Miracle-dz/UniFAR-FTUs huggingface dataset:
Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing.
Kidney-induced systemic tolerance of heart allografts in mice

In swine and nonhuman primates, kidney allografts can induce tolerance of heart allografts, leading to their long-term, immunosuppression-free survival. We refer to this phenomenon as kidney-induced cardiac allograft tolerance (KICAT). In this study, we have developed a murine model for KICAT to determine the underlining cellular/molecular mechanisms. Here, we show that spontaneously accepted DBA/2J kidneys in C57BL/6 recipients induce systemic tolerance that results in the long-term acceptance of DBA/2J heart allografts but not third-party cardiac allografts. The state of systemic tolerance of hearts was established 2 weeks after transplantation of the kidney, after which time, the kidney allograft is no longer required. Depletion of Foxp3+ T cells from these mice precipitated rejection of the heart allografts, indicating that KICAT is dependent on Treg function. Acceptance of kidney allografts and cotransplanted heart allografts did not require the thymus. In conclusion, these data show that kidney allografts induce systemic, donor-specific tolerance of cardiac allografts via Foxp3 cells, and that tolerance is independent of the thymus and continued presence of the kidney allograft. This experimental system should promote increased understanding of the tolerogenic mechanisms of the kidney.
Systematic review of economic evaluation studies on preconception care interventions

Abstract Implementation of preconception care interventions have been encouraged for improving maternal and child health outcomes; therefore, evidence on their cost-effectiveness is needed. We conducted the systematic review to examine the efficiency of those interventions by collecting evidence from published economic evaluation studies. Out of 14 included studies, almost all (12/14) were in high-income countries. All studies were not cost-utility analysis with genetic disease screening and diabetes management were the common interventions for evaluating their efficiency during preconception period. Preconception care interventions are likely to be cost-effective, especially in low-income countries which incremental benefits had a greater return than developed nations.
Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer.

Importance Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown. Objective To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer. Design, Setting, and Participants This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018. Exposures Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day. Main Outcomes and Measures Overall survival (OS) and progression-free survival (PFS). Results Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee. Conclusions and Relevance Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms.
Distinct binding and signaling activity of Acthar Gel compared to other melanocortin receptor agonists

Abstract Purpose To compare the binding and agonistic activity of Acthar® Gel and synthetic melanocortin receptor (MCR) agonists and examine how the activity of select agonists affects the in vivo production of corticosterone. Materials and Methods In vitro binding was determined using concentration-dependent displacement of the ligand [125I]Nle4, D-Phe7-α-melanocyte-stimulating hormone (α-MSH) on cells expressing MC1R, MC3R, MC4R, or MC5R. Functional activity was determined using a time-resolved fluorescence cyclic adenosine monophosphate (cAMP) assay in cells expressing MC1R, MC2R, MC3R, MC4R, or MC5R. In vivo corticosterone analyses were performed by measuring plasma corticosterone levels in Sprague Dawley rats. Results Acthar Gel and synthetic MCR agonists exhibited the highest binding at MC1R, lowest binding at MC5R, and moderate binding at MC3R and MC4R. Acthar Gel stimulated the production of cAMP in all 5 MCR-expressing cell lines, with MC2R displaying the lowest level of full agonist activity, 3-, 6.6-, and 10-fold lower than MC1R, MC3R, and MC4R, respectively. Acthar Gel was a partial agonist at MC5R. The synthetic MCR agonists induced full activity at all 5 MCRs, with the exception of α-MSH having no activity at MC2R. Acthar Gel treatment had less of an impact on in vivo production of corticosterone compared with synthetic ACTH1-24 depot. Conclusions Acthar Gel bound to and activated each MCR tested in this study, with partial agonist activity at MC5R and the lowest level of full agonist activity at MC2R, which distinguished it from synthetic MCR agonists. The minimal activity of Acthar Gel at MC2R corresponded to lower endogenous corticosteroid production.
Changes in Lung Cancer Treatment as a Result of the Coronavirus Disease 2019 Pandemic.

Changes in Lung Cancer Treatment as a Result of the Coronavirus Disease 2019 Pandemic Patients with cancer have higher mortality rates from coronavirus disease 2019 (COVID-19),1-4 particularly those with lung cancer.5 Therefore, efforts are ongoing to limit exposure of these patients to the health care system. As a result, the COVID-19 pandemic has changed cancer care provision, but the extent and type of these changes are unknown. The goal of this study was to evaluate the changes in lung cancer treatment during the COVID-19 pandemic.
Delayed Fulminant Hepatic Failure from Dydrogesterone-Related In Vitro Fertilization Therapy Requiring Liver Transplantation During Pregnancy

Patient: Female, 35-year-old Final Diagnosis: Fulminant liver failure Symptoms: Coagulopathy • hepatic encephalopathy • jaundice Medication:— Clinical Procedure: Liver transplantation Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: Drug-induced liver failure is a rare complication of pregnancy and occasionally requires liver transplantation. However, fulminant liver failure arising from in vitro fertilization (IVF) therapy involving progestogens (e.g. dydrogesterone) is extremely rare and has not been reported in pregnancy. Furthermore, dydrogesterone-mediated hepatic dysfunction has not previously necessitated liver transplantation and is usually conservatively managed. We report the first Australian case of a pregnant woman with delayed fulminant liver failure and in utero fetal death requiring a liver transplant from dydrogesterone use. Case Report: A 35-year-old multiparous (G5P2) woman presented with painless jaundice and transaminitis (alanine amino-transferase and aspartate aminotransferase of 2800 U/L and 2990 U/L respectively). She was pregnant at 14 weeks’ gestation after successful IVF in Thailand four months before involving dydrogesterone therapy. She was diagnosed with delayed, subfulminant liver failure arising from previous dydrogesterone use. Initially, she was not encephalopathic and conservative management strategies were instituted. Her hepatic dysfunction progressed and she deteriorated clinically with encephalopathy, necessitating an emergent liver transplantation. Fetal death was confirmed in utero four days before transplantation. A combined orthotopic liver transplant and hysterotomy with fetal evacuation were performed without complication. Conclusions: Fulminant liver failure in pregnancy due to idiosyncratic drug reactions are rare. Dydrogesterone may cause significant, albeit delayed, liver dysfunction in pregnancy necessitating the need for liver transplantation. Early recognition of progressive liver failure despite best supportive care efforts should prompt early considerations for liver transplantation. Delays in liver transplantation with prolonged hyperbilirubinemia and coagulopathy may exacerbate fetal death in utero.
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes

Blood-based epigenetic markers differentiate metformin responsiveness and tolerance in patients recently diagnosed with type 2 diabetes. How to mete out metformin Metformin is the most commonly used drug to treat type 2 diabetes (T2D), though not all patients respond to it, and still, others do not tolerate it. García-Calzón et al. analyzed genome-wide DNA methylation in the blood of drug-naïve patients who were recently diagnosed with T2D. They found that DNA methylation at specific loci associated with future metformin response or tolerance, respectively, across multiple cohorts. These epigenetic markers may have theranostic potential regarding which patients should receive metformin. Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associated with a higher risk of not responding to or not tolerating metformin with odds ratios between 1.43 and 3.09 per 1-SD methylation increase. Methylation risk scores (MRSs) of the 11 identified sites differed between glycemic responders and nonresponders with areas under the curve (AUCs) of 0.80 to 0.98. MRSs of the 4 sites associated with future metformin intolerance generated AUCs of 0.85 to 0.93. Some of these blood-based methylation markers mirrored the epigenetic pattern in adipose tissue, a key tissue in diabetes pathogenesis, and genes to which these markers were annotated to had biological functions in hepatocytes that altered metformin-related phenotypes. Overall, we could discriminate between glycemic responders/nonresponders and participants tolerant/intolerant to metformin at diagnosis by measuring blood-based epigenetic markers in drug-naïve patients with T2D. This epigenetics-based tool may be further developed to help patients with T2D receive optimal therapy.
An Anatomic Study on the Maxillary Sinus Mucosal Thickness and the Distance between the Maxillary Sinus Ostium and Sinus Floor for the Maxillary Sinus Augmentation

Background and objectives: The average rate of chronic sinusitis after maxillary implantation was approximately 5.1%. However, the evidence of predictive risk factors for sinusitis after implantation is lacking. The aim of this study was to perform an anatomic study on the maxillary sinus mucosal thickness (MSMT), the distance between the maxillary sinus ostium and sinus floor (MOD), and the MSMT/MOD ratio as a preoperative risk indicator for sinusitis after maxillary dental implantation. Materials and Methods: Between October 2008 and October 2019, all patients referred to the otolaryngology department were included in this study. A total of 120 patients were enrolled. The 95 patients who received no treatment prior to implantation were classified into Group A, the 16 patients who used antibiotics before implantation were classified into Group B, and the patients who had implants inserted after functional endoscopic sinus surgery were classified into Group C. The MSMT, MOD, MSMT/MOD ratio, anatomical factors associated with ostial obstruction, and the occurrence of postoperative sinusitis were reviewed. Results: There were significant group differences in MSMT (Group A vs. Group B, p = 0.001; Group B vs. Group C, p = 0.003; Group C vs. Group A, p < 0.0001). The MOD showed no significant difference among the three groups. The MSMT/MOD ratio showed significant differences between Groups A and B (p = 0.001), B and C (p < 0.0001), and C and A (p < 0.0001). Conclusions: It is important to check not only the proportion of the maxillary sinus occupying lesion, but also the status of the maxillary sinus osteomeatal complex when making therapeutic decisions. In addition, collaboration between dentists and otolaryngologists could improve outcomes in patients with maxillary sinus lesions.
Super-Resolution Microscopy Reveals a Direct Interaction of Intracellular Mycobacterium tuberculosis with the Antimicrobial Peptide LL-37

The antimicrobial peptide LL-37 inhibits the growth of the major human pathogen Mycobacterium tuberculosis (Mtb), but the mechanism of the peptide–pathogen interaction inside human macrophages remains unclear. Super-resolution imaging techniques provide a novel opportunity to visualize these interactions on a molecular level. Here, we adapt the super-resolution technique of stimulated emission depletion (STED) microscopy to study the uptake, intracellular localization and interaction of LL-37 with macrophages and virulent Mtb. We demonstrate that LL-37 is internalized by both uninfected and Mtb infected primary human macrophages. The peptide localizes in the membrane of early endosomes and lysosomes, the compartment in which mycobacteria reside. Functionally, LL-37 disrupts the cell wall of intra- and extracellular Mtb, resulting in the killing of the pathogen. In conclusion, we introduce STED microscopy as an innovative and informative tool for studying host–pathogen–peptide interactions, clearly extending the possibilities of conventional confocal microscopy.
Latent class trajectories of infant temperament and associations with problem behavior at two years of age

Abstract Individual differences in temperament have been well-described, but individual differences in temperament trajectories require elaboration. Specifically, it is unknown if subgroups of infants display different developmental patterns and if these patterns relate to later behavioral problems. The aims were to identify distinct developmental patterns in broad dimensions of temperament among typically developing infants, to determine whether these developmental patterns differ by sex, to evaluate how developmental patterns within each dimension of temperament relate to developmental patterns within other dimensions of temperament, and to determine whether developmental patterns of infant temperament are associated with internalizing and externalizing behavior at 2 years of age. Data from the longitudinal Alberta Pregnancy Outcomes and Nutrition study (n = 1,819) were used to model latent class trajectories of parent-reported infant temperament at 3, 6, and 12 months. Four to five unique latent trajectories were identified within each temperament dimension. Sex was not associated with trajectory groups. Developmental coordination was observed between trajectories of negative emotionality and regulatory capacity, and between regulatory capacity and positive affect, but not between positive affect and negative emotionality. Negative emotionality and regulatory capacity predicted internalizing and externalizing behavior. Patterns of development in infant temperament, and not just intensity of temperament, contribute toward later problem behavior.
The role of pathogens in determining plant recruitment and distribution patterns in a western Amazonian floodplain

The Janzen and Connell (J-C) hypothesis proposes that plant pathogens and herbivores regulate recruitment of tropical plants near conspecific adults. For 150 days disease incidence, insect damage and mortality rates were monitored on the most common tree species in western Amazonia, Iriartea deltoidea (Arecaceae). The causal agents of diseases, insect damage and mortality in I. deltoidea seedlings and juveniles were identified and classified into six groups based on their effects on the plant. The proportion of dead seedlings (induced by several different pathogens, insects and random causes) decreased with distance from fruiting adults, consistent with predictions from the J-C hypothesis. Each causal agent of plant damage had a different distance-dependent spatial structure on plant mortality. Stem borers produced high mortality near fruiting trees and the highest mortality rate for young seedlings. Fungal diseases (foliar spots and wilting) and insect herbivory present in most evaluated plants, at all distances, induced initially low mortality rates that increased over time. Logistic regression analysis was used to separate distance and density effects on juvenile mortality and infection rates.
Treatment modalities for Korean patients with unilateral hemifacial microsomia according to Pruzansky–Kaban types and growth stages

Objective To investigate the treatment modalities (Tx-Mods) for patients with unilateral hemifacial microsomia (UHFM) according to Pruzansky–Kaban types and growth stages. Methods The samples consisted of 82 Korean UHFM patients. Tx-Mods were defined as follows Tx-Mod-1, growth observation due to mild facial asymmetry; Tx-Mod-2, unilateral functional appliance; Tx- Mod-3, fixed orthodontic treatment; Tx-Mod-4, growth observation due to a definite need for surgical intervention; Tx-Mod-5, unilateral mandibular or bimaxillary distraction osteogenesis (DO); Tx-Mod-6, maxillary fixation using LeFort I osteotomy and mandibular DO/sagittal split ramus osteotomy; Tx- Mod-7, orthognathic surgery; and Tx-Mod-8, costochondral grafting. The type and frequency of Tx-Mod, the number of patients who underwent surgical procedures, and the number of surgeries that each patient underwent, were investigated. Results The degree of invasiveness and complexity of Tx-Mod increased, with an increase in treatment stage and Pruzansky–Kaban type (initial < final; [I, IIa] < [IIb, III], all p < 0.001). The percentage of patients who underwent surgical procedures increased up to 4.2 times, with an increase in the Pruzansky–Kaban type (I, 24.1%; IIa, 47.1%; IIb, 84.4%; III, 100%; p < 0.001). However, the mean number of surgical procedures that each patient underwent showed a tendency of increase according to the Pruzansky–Kaban types (I, n = 1.1; IIa, n = 1.5; IIb, n = 1.6; III, n = 2.3; p > 0.05). Conclusions These findings might be used as basic guidelines for successful treatment planning and prognosis prediction in UHFM patients.
A system for designing removable partial dentures using artificial intelligence. Part 1. Classification of partially edentulous arches using a convolutional neural network.

PURPOSE The purpose of this study was to develop a method for classifying dental arches using a convolutional neural network (CNN) as the first step in a system for designing removable partial dentures. METHODS Using 1184 images of dental arches (maxilla: 748 images; mandible: 436 images), arches were classified into four arch types: edentulous, intact dentition, arches with posterior tooth loss, and arches with bounded edentulous space. A CNN method to classify images was developed using Tensorflow and Keras deep learning libraries. After completion of the learning procedure, the diagnostic accuracy, precision, recall, F-measure and area under the curve (AUC) for each jaw were calculated for diagnostic performance of learning. The classification was also predicted using other images, and percentages of correct predictions (PCPs) were calculated. The PCPs were compared with the Kruskal-Wallis test (p = 0.05). RESULTS The diagnostic accuracy was 99.5% for the maxilla and 99.7% for the mandible. The precision, recall, and F-measure for both jaws were 0.25, 1.0 and 0.4, respectively. The AUC was 0.99 for the maxilla and 0.98 for the mandible. The PCPs of the classifications were more than 95% for all types of dental arch. There were no significant differences among the four types of dental arches in the mandible. CONCLUSIONS The results of this study suggest that dental arches can be classified and predicted using a CNN. Future development of systems for designing removable partial dentures will be made possible using this and other AI technologies.