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ABSTRACTPatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.

Abstract The early detection of initial dental caries enables preventive treatment, and bitewing radiography is a good diagnostic tool for posterior initial caries. In medical imaging, the utilization of deep learning with convolutional neural networks (CNNs) to process various types of images has been actively researched, with promising performance. In this study, we developed a CNN model using a U-shaped deep CNN (U-Net) for caries detection on bitewing radiographs and investigated whether this model can improve clinicians’ performance. The research complied with relevant ethical regulations. In total, 304 bitewing radiographs were used to train the CNN model and 50 radiographs for performance evaluation. The diagnostic performance of the CNN model on the total test dataset was as follows: precision, 63.29%; recall, 65.02%; and F1-score, 64.14%, showing quite accurate performance. When three dentists detected caries using the results of the CNN model as reference data, the overall diagnostic performance of all three clinicians significantly improved, as shown by an increased sensitivity ratio (D1, 85.34%; D1′, 92.15%; D2, 85.86%; D2′, 93.72%; D3, 69.11%; D3′, 79.06%; p

Global energy demand has unquestionably increased significantly in recent years. Nowadays, industries are very aware of global warming, and to save the environment, they produce green products with energy consumption. Day by day, energy use is increasing due to population, end-use markets of construction, transportation, industry, etc. But the energy limit is finite, whereas the daily use is rising, so the price is increasing. In this study, two situations have been shown in two models with renewable energy consumption. Model 1 analyzes the manufacturer and retailer’s optimal green quality and sales price in two-echelon supply chain systems with centralized and decentralized cases. In this case, the retailer sells their products through three different channels: online, offline, and buy-online-pickup-in store, with three different selling prices. In Model 2, Manufacturer 1 and Manufacturer 2 produce green and regular products with renewable energy consumption. In this case, both manufacturers sell their products through three different channels: online, offline, and buy-online-pickup-in store, with three different selling prices. There is competition between substitutable products with respect to green quality and the selling price of the products. A hybrid channel policy is studied here to maximize the total profit with considering corporate social responsibility under renewable energy consumption. The study has been analyzed mathematically. The classical optimization approach and game theory are applied here to find the optimal values of procurement cost, selling price, and green quality development cost. A numerical study shows that the centralized system gives a better result to the manufacturer than the decentralized system. When the demand is a power function of the selling price, the manufacturer producing eco-friendly products gains 0.99% more profit than the conventional product. This result shows that manufacturers creating eco-friendly products motivate other manufacturers to make eco-friendly products.

The central symptom of autism spectrum disorder (ASD) is deficiency in social communication, which is generally viewed as being caused by pragmatic impairment (PI). PI is difficulty in using language appropriately in social situations. Studies have confirmed that PI is the result of neurological, cognitive, linguistic, and sensorimotor dysfunctions involving intricately intertwined factors. To elucidate the whole picture of this impairment, an approach from a multifaceted perspective fusing those factors is necessary. To this end, comprehensive PI mapping is a must, since no comprehensive mapping has yet been developed. The aim of this research is to present a model of annotation scheme development and corpus construction to efficiently visualize and quantify for statistical investigation occurrences of PI, which enables comprehensive mapping of PI in the spoken language of Japanese ASD individuals. We constructed system networks (lexicogrammatical option systems speakers make choices from) in the theoretical framework of Systemic Functional Linguistics, from which we developed an annotation scheme to comprehensively cover PI. Since system network covers all possible lexicogrammatical choices in linguistic interaction, it enables a comprehensive view of where and in what lexicogrammar PI occurs. Based on this annotation scheme, we successfully developed the Corpus of ASD + Typically Developed Spoken Language consisting of texts from 1,187 audiotaped tasks performed by 186 ASD and 106 typically developed subjects, accommodating approximately 1.07 million morphemes. Moreover, we were successful in the automatization of the annotation process by machine learning, accomplishing a 90 percent precision rate. We exemplified the mapping procedure with a focus on the spoken use of negotiating particles. Our model corpus is applicable to any language by incorporating our method of constructing the annotation scheme, and would give impetus to defining PI from a cross-linguistic point of view, which is needed because PI of ASD reflects cross-linguistic differences.

Abstract Backgrounds Whether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD). Method In this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013–2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team. Results Caregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66–3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00–1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD. Limitations Modest sample size for a total population study. Conclusions Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.

Background: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions: We expect to provide scientific evidence on the effectiveness of health counselling.

Abstract Background Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. Methods We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0–5, 6–11, and 12–18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. Results In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. Limitations It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects’ age. Conclusions There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.

Abstract Background This study, by using a variable-controlled survey model, sought to compare clinical decisions made by dentists with different clinical backgrounds in South Korea regarding teeth with apical periodontitis and to identify factors that influenced decision-making. Methods A questionnaire with 36 questions about identical patient information, clinical signs, and symptoms was filled out by participants. Each question referred to a radiograph that had been manipulated using computer software in order to control tooth-related factors. Participants were instructed to record their demographic information and choose the ideal treatment option related to each radiograph. Simple and multivariable logistic regression analyses (p

Background and study aims Antireflux mucosectomy (ARMS) and antireflux mucosal ablation (ARMA) are new endoscopic procedures for patients with gastroesophageal reflux disease (GERD). We conducted a meta-analysis to systematically assess the feasibility, clinical success, and safety of these procedures. Patients and methods We searched Embase, PubMed, and Cochrane Central from inception to October 2020. Overlapping reports, animal studies, and case reports were excluded. Our primary outcomes were clinical success and adverse events (AEs). Secondary outcomes included technical success, endoscopic esophagitis, 24-hour pH monitoring, and proton pump inhibitor (PPI) use. A random effects model was used to pool data. Results In total, 15 nonrandomized studies (12 ARMS, n = 331; 3 ARMA, n = 130) were included; 10 were conducted in patients with refractory GERD. The technical success rate was 100 %. The pooled short-term (first assessment within the first 6 months), 1-year, and 3-year clinical success rates were 78 % (95 % confidence interval [95 %CI] 70 %–85 %), 72% (95 %CI 47 %–92 %), and 73 % (95 %CI 65 %–81 %), respectively. ARMS and ARMA yielded similar clinical success. The proportion of patients off PPIs at 1 year was 64 % (95 %CI 52 %–75 %). There were significant drops (P

Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus (VpAHPND) has been reported in commodity shrimp, but the potential risk of its global spread via frozen shrimp in the shrimp trade is yet to be fully explored. We hypothesized that frozen shrimp with AHPND could be a source of VpAHPND transmission; thus, the infectivity of frozen shrimp with AHPND was evaluated using a shrimp bioassay. To prepare infected frozen shrimp, 12 Penaeus vannamei (average weight, 2 g) were exposed to VpAHPND by immersion in water with a VpAHPND concentration of 1.55 × 107 CFU mL−1; once dead, the shrimp were stored at −80 °C for further analysis. After two weeks, a PCR assay was used to confirm AHPND positivity in frozen shrimp (n = 2), and VpAHPND was reisolated from the hepatopancreases of these shrimp. For the infectivity test, 10 P. vannamei (average weight, 4 g) were fed with the hepatopancreases of VpAHPND -infected frozen shrimp (n = 10). After feeding, 70% of the shrimp died within 118 h, and the presence of VpAHPND was confirmed using a PCR assay and histopathology examination; moreover, VpAHPND was successfully reisolated from the hepatopancreases of the dead shrimp. We are the first to evaluate the potential transmissibility of VpAHPND in frozen shrimp, and our results suggest that frozen shrimp with AHPND are a potential source of disease spreading between countries during international trade.

Purpose: To introduce cases of the use, as patch grafts, of stromal lenticules obtained by small incision lenticule extraction (SMILE) surgery. Observations: Case 1 was a 79-year-old man who presented with Ahmed-valve-tube exposure in his left eye. His uncorrected visual acuity (UCVA) was 20/40, best-corrected visual acuity (BCVA) 20/32, and intraocular pressure (IOP) 11 mmHg. He was treated with stromal lenticule patch that had been extracted by SMILE surgery. The patch was positioned underneath of the conjunctiva and sutured to it. At postoperative 8 months, the graft site was well maintained without Ahmed valve-tube exposure, the UCVA was 20/32, BCVA 20/20, and IOP 12 mmHg.Case 2 was a 60-year-old man who presented with Ahmed-valve-tube exposure in his right eye. His UCVA was finger-count (FC) 30 cm, his BCVA 20/125, and his IOP 14 mmHg. He was treated with stromal lenticule patch by the same method as employed in case 1. At postoperative 10 days, tube re-exposure and displacement of the Ahmed valve external plate toward the limbus area occurred due to loosening of the anchoring suture. So, we removed the Ahmed valve device, which had been implanted in the supero-temporal area, and performed new Ahmed valve implantation, with a stromal lenticule flap instead of a partial scleral flap, in the supero-nasal area. As of 6 months post-reoperation, the patient was stable, with UCVA 20/200, BCVA 20/40 and IOP 13 mmHg.Case 3 was a 74-year-old man who presented with bullous keratopathy in his right eye, which was blind. Due to severe adhesions, his conjunctiva could not cover the entire cornea. Therefore, we performed a stromal lenticule patch graft with conjunctival advance flap. At postoperative 3 months, the patient's right eye was stable, without displacement or melting of the lenticule graft. Conclusions & importance: It is suggested that the stromal lenticule, with its biocompatibility, sufficient strength, ease of handling and low cost, is a useful patch graft for various therapeutic purposes in the ophthalmic field. Keywords: Stromal lenticule, Patch graft, Ahmed valve tube exposure, Bullous keratopathy

Abstract Background To report a case of impending extrusion of Ex-PRESS shunt treated by shunt-position adjustment. Case presentation A 56-year-old Asian woman presented with impending extrusion and malposition of Ex-PRESS shunt in her left eye. The bleb of the left eye was shallow and diffuse. In the past, the patient was treated by Ex-PRESS shunt implantation under the scleral flap in both eyes. There had been no Ex-PRESS shunt-related complication in her right eye, and she reported no history of left-eye trauma. Based on these findings, we hypothesized that the source of the left-eye problem was a loosely fixed Ex-PRESS shunt spur. It was thought, furthermore, that this inadequate scleral resistance during the Ex-PRESS shunt implantation was due to the low scleral rigidity resulting from high myopia and insufficient maintenance of the anterior chamber. We proceeded to make an incision in the area adjacent to the Ex-PRESS shunt using a super sharp blade. The shunt was then pushed into the anterior chamber with forceps, and the spur was fixed firmly. Pushing the shunt to the anterior chamber was found to have been sufficient to fix it firmly. In fact, when the sclera was palpated with a sponge, aqueous outflow was observed with no shunt displacement. Postoperative intraocular pressure (IOP) was managed well, and the bleb had formed with diffuse, prominent shapes. The Ex-PRESS shunt was well sustained with good positioning. Conclusions When an Ex-PRESS shunt operation is performed on a patient who shows a tendency for low scleral rigidity, shunt implantation should be accomplished carefully and with force adequate for firm spur fixation.

The improvement of position estimation accuracy is a very important factor in various radar applications. This paper focuses on two-dimensional (2-D) location estimation in radar surveillance using leaky coaxial cables. A leaky coaxial cable is a kind of antenna and has recently attracted attention as a powerful tool for vehicle detection and as an intrusion detection sensor for perimeter security. We derive the Cramér-Rao bound (CRB) for a leaky coaxial cable sensing application and introduce the CRB ellipsoid to evaluate the accuracy of the 2-D location estimation of an object. The diameter and angle of a CRB ellipsoid indicates its error distribution. A leaky coaxial cable has an outer conductor with periodic slots. Its slot pattern determines the radiation characteristics such as the beam angle and harmonic radiation. We focus on the slot pattern to improve the estimation accuracy. Numerical analyses show that a slot pattern generating multi-beams improves the accuracy while single radiation is preferred for general use in communication applications. [ABSTRACT FROM PUBLISHER]

This study aims to obtain sufficient corneal endothelial cells for regenerative application. We examined the combinatory effects of Rho-associated kinase (ROCK) inhibitor Y-27632 and mesenchymal stem cell-derived conditioned medium (MSC-CM) on the proliferation and senescence of rabbit corneal endothelial cells (rCECs). rCECs were cultured in a control medium, a control medium mixed with either Y-27632 or MSC-CM, and a combinatory medium containing Y-27632 and MSC-CM. Cells were analyzed for morphology, cell size, nuclei/cytoplasmic ratio, proliferation capacity and gene expression. rCECs cultured in a combinatory culture medium showed a higher passage number, cell proliferation, and low senescence. rCECs on collagen type I film showed high expression of tight junction. The cell proliferation marker Ki-67 was positively stained either in Y-27632 or MSC-CM-containing media. Genes related to cell proliferation resulted in negligible changes in MKI67, CIP2A, and PCNA in the combinatory medium, suggesting proliferative capacity was maintained. In contrast, all of these genes were significantly downregulated in the other groups. Senescence marker β-galactosidase-positive cells significantly decreased in either MSC-CM and/or Y-27632 mixed media. Senescence-related genes downregulated LMNB1 and MAP2K6, and upregulated MMP2. Cell cycle checkpoint genes such as CDC25C, CDCA2, and CIP2A did not vary in the combinatory medium but were significantly downregulated in either ROCK inhibitor or MSC-CM alone. These results imply the synergistic effect of combinatory culture medium on corneal endothelial cell proliferation and high cell number. This study supports high potential for translation to the development of human corneal endothelial tissue regeneration.

Signal transducers and activators of transcription 6 (STAT6) play a crucial role in the transactivation of IL-4 and IL-13, which might be involved in the pathogenesis of atopic dermatitis (AD). We herein reported that the IgE-mediated late-phase reaction significantly decreased in STAT6-deficient (STAT6-/-) mice in AD model mice induced by intravenous injection of monoclonal anti-dinitrophenyl (DNP)-IgE antibody and subsequent skin testing with dinitrofluorobenzene. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for STAT6 could be introduced in vivo as decoy cis elements to bind the transcriptional factor and block the gene activation contributing to the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODNs), but not scramble decoy ODN after sensitization by anti-DNP-IgE antibody, had a significant inhibitory effect on not only STAT6 binding to nuclei but also on the late-phase response. A histological analysis revealed that both edema and the infiltration of neutrophils and eosinophils significantly decreased in STAT6 decoy ODN-transfected mice. To examine the mechanism of the in vivo effect of STAT6 decoy ODN, we employed an in vitro mast cells culture system. After IgE receptor engagement, mast cells transfected by STAT6 decoy ODN exhibited normal histamine release, but their cytokine release (TNF-a, IL-6) markedly decreased. We herein report the first successful in vivo transfer of STAT6 decoy ODN to reduce the late-phase reaction, thereby providing a new therapeutic strategy for AD.Gene Therapy (2004) 11, 1753-1762. doi:10.1038/sj.gt.3302341; Published online 12 August 2004 [ABSTRACT FROM AUTHOR]

We herein demonstrate that STAT6 plays an important role in the induction of not only acute contact hypersensitivity (CHS), but also chronic CHS in a mouse model using STAT6-deficient (STAT6-/-) mice. We, therefore, determine whether synthetic double-stranded DNA with a high affinity for STAT6 can be introduced in vivo as a decoy cis element to bind the transcriptional factor and block the induction of not only acute CHS but also chronic CHS. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), after the induction of 2,4,6-trinitrochlorobenzene or other haptens had a significant inhibitory effect on the induction of both acute CHS and chronic CHS. We thus examined the mechanism of the in vivo effect of the transfection of STAT6 decoy ODN in both acute and chronic CHS. In the histological analysis, the infiltration of eosinophils and degranulated mast cells, and the production of IL-4, IL-6 and eotaxin, but not IFN-?in the extracts from challenged skin significantly decreased by the transfection of STAT6 decoy ODN. We herein report the first successful in vivo transfer of STAT6 decoy ODN to inhibit acute and chronic CHS, thus providing a new therapeutic strategy not only for the treatment of CHS but also for atopic dermatitis.Gene Therapy (2004) 11, 1763-1771. doi:10.1038/sj.gt.3302345; Published online 12 August 2004 [ABSTRACT FROM AUTHOR]

Postpartum depression is a severe emotional and mental disorder that involves maternal care defects and psychiatric illness. Postpartum depression is closely associated with a combination of physical changes and physiological stress during pregnancy or after parturition in stress-sensitive women. Although postpartum depression is relatively well known to have deleterious effects on the developing fetus, the influence of genetic risk factors on the development of postpartum depression remains unclear. In this study, we discovered a novel function of T cell death-associated gene 51 (TDAG51/PHLDA1) in the regulation of maternal and depressive-like behavior. After parturition, TDAG51-deficient dams showed impaired maternal behavior in pup retrieving, nursing and nest building tests. In contrast to the normal dams, the TDAG51-deficient dams also exhibited more sensitive depressive-like behaviors after parturition. Furthermore, changes in the expression levels of various maternal and depressive-like behavior-associated genes regulating neuroendocrine factor and monoamine neurotransmitter levels were observed in TDAG51-deficient postpartum brain tissues. These findings indicate that TDAG51 plays a protective role against maternal care defects and depressive-like behavior after parturition. Thus, TDAG51 is a maternal care-associated gene that functions as a crucial regulator of maternal and depressive-like behavior after parturition.

Osteoblasts, which are bone-forming cells, play pivotal roles in bone modeling and remodeling. Osteoblast differentiation, also known as osteoblastogenesis, is orchestrated by transcription factors, such as runt-related transcription factor 1/2, osterix, activating transcription factor 4, special AT-rich sequence-binding protein 2 and activator protein-1. Osteoblastogenesis is regulated by a network of cytokines under physiological and pathophysiological conditions. Osteoblastogenic cytokines, such as interleukin-10 (IL-10), IL-11, IL-18, interferon-γ (IFN-γ), cardiotrophin-1 and oncostatin M, promote osteoblastogenesis, whereas anti-osteoblastogenic cytokines, such as tumor necrosis factor-α (TNF-α), TNF-β, IL-1α, IL-4, IL-7, IL-12, IL-13, IL-23, IFN-α, IFN-β, leukemia inhibitory factor, cardiotrophin-like cytokine, and ciliary neurotrophic factor, downregulate osteoblastogenesis. Although there are gaps in the body of knowledge regarding the interplay of cytokine networks in osteoblastogenesis, cytokines appear to be potential therapeutic targets in bone-related diseases. Thus, in this study, we review and discuss our osteoblast, osteoblast differentiation, osteoblastogenesis, cytokines, signaling pathway of cytokine networks in osteoblastogenesis.

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2–76.9% and 24.0–26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0–13.6% higher), trabecular bone volume fraction (32.5–38.1% higher), trabecular thickness (8.4–9.0% higher), and trabecular number (25.5–26.7% higher) and decreased trabecular spacing (9.3–10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8–65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5–Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

This study aimed to evaluate one-year radiographic healing after endodontic microsurgery using CBCT with modified PENN 3D criteria and to compare the outcome with results evaluated using Molven’s criteria. A total of 107 teeth from 96 patients were evaluated one year after endodontic microsurgery by using CBCT scans with modified PENN 3D criteria and periapical radiographs with Molven’s criteria. Both preoperative and postoperative lesion volumes were calculated using ITK-SNAP (free software). Radiographic healing assessment using periapical radiographs and CBCT images, and preoperative and postoperative lesion volume measurements were performed independently by two examiners. The assessment using Molven’s criteria resulted in 75 complete healings, 18 incomplete healings, eight uncertain healings, and six unsatisfactory healings. Based on modified PENN 3D criteria, 64 teeth were categorized as complete healing, 29 teeth as limited healing, six teeth as uncertain healing, and eight teeth as unsatisfactory healing. With the one-year follow-up, CBCT scans showed a lower healing tendency than did periapical radiography. The volumes of apical radiolucency after the surgery were reduced by 77.7% on average at one-year follow up.

Computer programmers require various instructive information during coding and development. Such information is dispersed in different sources like language documentation, wikis, and forums. As an information exchange platform, programmers broadly utilize Stack Overflow, a Web-based Question Answering site. In this paper, we propose a recommender system which uses a supervised machine learning approach to investigate Stack Overflow posts to present instructive information for the programmers. This might be helpful for the programmers to solve programming problems that they confront with in their daily life. We analyzed posts related to two most popular programming languages—Python and PHP. We performed a few trials and found that the supervised approach could effectively manifold valuable information from our corpus. We validated the performance of our system from human perception which showed an accuracy of 71%. We also presented an interactive interface for the users that satisfied the users’ query with the matching sentences with most instructive information.

[This corrects the article DOI: 10.1371/journal.pone.0199590.].

90Sr, which was released into the atmosphere and the ocean following the Chernobyl and Fukushima Daiichi nuclear power plant disasters, is an important nuclear fission element. Compounds that inhibit the absorption of 90Sr into the bloodstream and enhance its elimination can be beneficial in decreasing the absorbed radiation dose in people exposed to 90Sr. Recently, we prepared complexes of myo-inositol-hexakisphosphate (InsP6) with zinc or lanthanum as decorporation agents. These complexes, called Zn-InsP6 and La-InsP6 respectively, are insoluble in water and can potentially chelate additional metal cations. Hypothesizing that these complexes can assist the excretion of 90Sr from the body, we evaluated them using 85Sr instead of 90Sr. In in vitro binding experiments, Zn-InsP6 showed higher strontium adsorption capacity than La-InsP6. We then performed in vivo biodistribution experiments of Zn-InsP6 in mice after oral administration of 85SrCl2. Mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity than mice in a non-treatment control group. Zn-InsP6 adsorbed radiostrontium in the gastrointestinal tract, inhibited this ion's absorption into the bloodstream, and enhanced its excretion in the feces. Therefore, Zn-InsP6 appears to be a promising 90Sr "decorporation" agent.

The Autism Spectrum Screening Questionnaire (ASSQ) is equipped with good properties for screening the broader phenotype of autistic traits, but it is standardized for a limited age range-from 7 to 16 years. To contribute to the early detection of Autism Spectrum Disorder (ASD), particularly in high functioning children with ASD, likely to cause maladjustments during school age, the present study examined psychometric properties to apply the ASSQ to a younger age. We tested parents' ASSQ ratings for preschool children in clinical (N = 154, average age 60.77 months, range 55-72 months) and community settings (N = 1390, average age 60.53 months, range 57-68 months) in Japan. The results showed, just as in school-aged children, the ASSQ had reliability and validity as a screening instrument for preschool children in community settings. A cut-off of 7 with sensitivity of 0.93 and specificity of 0.84 is recommended for community screening. Still, based on the current study with a clinical group, an optimal cut-off score with high sensitivity and high specificity for parents' ASSQ ratings could not be established. The clinicians should be reminded that the ASSQ is a screening instrument, not a diagnosing instrument. Also, this result suggest multi-faceted evaluation is necessary in clinical settings, for example, the addition of teachers' ratings.