Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-contained deep learning-based boosting of 4D cone-beam CT reconstruction.

PURPOSE Four-dimensional cone-beam computed tomography (4D CBCT) imaging has been suggested as a solution to account for interfraction motion variability of moving targets like lung and liver during radiotherapy (RT) of moving targets. However, due to severe sparse view sampling artifacts, current 4D CBCT data lack sufficient image quality for accurate motion quantification. In the present paper, we introduce a deep learning-based framework for boosting the image quality of 4D CBCT image data that can be combined with any CBCT reconstruction approach and clinical 4D CBCT workflow. METHODS Boosting is achieved by learning the relationship between so-called sparse view pseudo-time-average CBCT images obtained by a projection selection scheme introduced to mimic phase image sparse view artifact characteristics and corresponding time-average CBCT images obtained by full view reconstruction. The employed convolutional neural network architecture is the residual dense network (RDN). The underlying hypothesis is that the RDN learns the appearance of the streaking artifacts that is typical for 4D CBCT phase images - and removes them without influencing the anatomical image information. After training the RDN, it can be applied to the 4D CBCT phase images to enhance the image quality without affecting the contained temporal and motion information. Different to existing approaches, no patient-specific prior knowledge about anatomy or motion characteristics is needed, that is, the proposed approach is self-contained. RESULTS Application of the trained network to reconstructed phase images of an external (SPARE challenge) as well as in-house 4D CBCT patient and motion phantom data set reduces the phase image streak artifacts consistently for all patients and state-of-the-art reconstruction approaches. Using the SPARE data set, we show that the root mean squared error compared to ground truth data provided by the challenge is reduced by approximately 50% while normalized cross correlation of reconstruction and ground truth is improved up to 10%. Compared to direct deep learning-based 4D CBCT to 4D CT mapping, our proposed method performs better because inappropriate prior knowledge about the patient anatomy and physiology is taken into account. Moreover, the image quality enhancement leads to more plausible motion fields estimated by deformable image registration (DIR) in the 4D CBCT image sequences. CONCLUSIONS The presented framework enables significantly boosting of 4D CBCT image quality as well as improved DIR and motion field consistency. Thus, the proposed method facilitates extraction of motion information from severely artifact-affected images, which is one of the key challenges of integrating 4D CBCT imaging into RT workflows.
Informant Discrepancies in Child Maltreatment Reporting: A Systematic Review

Potential informants on child maltreatment include the youth who has experienced the alleged maltreatment, and the youth’s caregivers, social workers and case files. When multiple informants are compared, they often disagree about whether or not a youth has experienced maltreatment. Such determinations are critical as endorsement—or lack of endorsement—of maltreatment can have significant consequences on the child’s safety, future living arrangements and referral for treatment and services. The current study provides a systematic review of the literature on informant discrepancies in child maltreatment. Three databases—PsychINFO, Web of Science, and PubMed—were used to identify studies for the review and 13 articles met inclusion criteria. Results showed that more youth tend to report physical, sexual and emotional abuse than seen in case files. By contrast, more case files include neglect than reported by youth. Implications and future directions are discussed.
Intent to Adopt Video-Based Integrated Mental Health Care and the Characteristics of its Supporters: Mixed Methods Study Among General Practitioners Applying Diffusion of Innovations Theory

Background Most people with common mental disorders, including those with severe mental illness, are treated in general practice. Video-based integrated care models featuring mental health specialist video consultations (MHSVC) facilitate the involvement of specialist mental health care. However, the potential uptake by general practitioners (GPs) is unclear. Objective This mixed method preimplementation study aims to assess GPs’ intent to adopt MHSVC in their practice, identify predictors for early intent to adopt (quantitative strand), and characterize GPs with early intent to adopt based on the Diffusion of Innovations Theory (DOI) theory (qualitative strand). Methods Applying a convergent parallel design, we conducted a survey of 177 GPs and followed it up with focus groups and individual interviews for a sample of 5 early adopters and 1 nonadopter. We identified predictors for intent to adopt through a cumulative logit model for ordinal multicategory responses for data with a proportional odds structure. A total of 2 coders independently analyzed the qualitative data, deriving common characteristics across the 5 early adopters. We interpreted the qualitative findings accounting for the generalized adopter categories of DOI. Results This study found that about one in two GPs (87/176, 49.4%) assumed that patients would benefit from an MHSVC service model, about one in three GPs (62/176, 35.2%) intended to adopt such a model, the availability of a designated room was the only significant predictor of intent to adopt in GPs (β=2.03, SE 0.345, P<.001), supporting GPs expected to save time and took a solution-focused perspective on the practical implementation of MHSVC, and characteristics of supporting and nonsupporting GPs in the context of MHSVC corresponded well with the generalized adopter categories conceptualized in the DOI. Conclusions A significant proportion of GPs may function as early adopters and key stakeholders to facilitate the spread of MHSVC. Indeed, our findings correspond well with increasing utilization rates of telehealth in primary care and specialist health care services (eg, mental health facilities and community-based, federally qualified health centers in the United States). Future work should focus on specific measures to foster the intention to adopt among hesitant GPs.
Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3

ABSTRACT The commensal bacterium Faecalibacterium prausnitzii plays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-α and exposed to F. prausnitzii culture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene after F. prausnitzii SN contact was validated both in vitro and in vivo. Our results showed that F. prausnitzii SN upregulates the expression of Dact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silenced Dact3 expression, the effect of F. prausnitzii SN was lost. Butyrate was identified as the F. prausnitzii effector responsible for Dact3 modulation. Dact3 upregulation was also validated in vivo in both healthy and inflamed mice treated with either F. prausnitzii SN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influences Dact3 expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacterium F. prausnitzii.
Intraguild predation between Pristionchus pacificus and Caenorhabditis elegans: a complex interaction with the potential for aggressive behaviour

Abstract The related nematodes Pristionchus pacificus and Caenorhabditis elegans both eat bacteria for nutrition and are therefore competitors when they exploit the same bacterial resource. In addition to competing with each other, P. pacificus is a predator of C. elegans larval prey. These two relationships together form intraguild predation, which is the killing and sometimes eating of potential competitors. In killing C. elegans, the intraguild predator P. pacificus may achieve dual benefits of immediate nutrition and reduced competition for bacteria. Recent studies of P. pacificus have characterized many aspects of its predatory biting behaviour as well as underlying molecular and genetic mechanisms. However, little has been explored regarding the potentially competitive aspect of P. pacificus biting C. elegans. Moreover, aggression may also be implicated if P. pacificus intentionally bites C. elegans with the goal of reducing competition for bacteria. The aim of this review is to broadly outline how aggression, predation, and intraguild predation relate to each other, as well as how these concepts may be applied to future studies of P. pacificus in its interactions with C. elegans.
N‐glycosylation of PD‐1 promotes binding of camrelizumab

PD‐1 is a highly glycosylated inhibitory receptor expressed mainly on T cells. Targeting of PD‐1 with monoclonal antibodies (MAbs) to block the interaction with its ligand PD‐L1 has been successful for the treatment of multiple tumors. However, polymorphisms at N‐glycosylation sites of PD‐1 exist in the human population that might affect antibody binding, and dysregulated glycosylation has been observed in the tumor microenvironment. Here, we demonstrate varied N‐glycan composition in PD‐1, and show that the binding affinity of camrelizumab, a recently approved PD‐1‐specific MAb, to non‐glycosylated PD‐1 proteins from E. coli is substantially decreased compared with glycosylated PD‐1. The structure of the camrelizumab/PD‐1 complex reveals that camrelizumab mainly utilizes its heavy chain to bind to PD‐1, while the light chain sterically inhibits the binding of PD‐L1 to PD‐1. Glycosylation of asparagine 58 (N58) promotes the interaction with camrelizumab, while the efficiency of camrelizumab to inhibit the binding of PD‐L1 is substantially reduced for glycosylation‐deficient PD‐1. These results increase our understanding of how glycosylation affects the activity of PD‐1‐specific MAbs during immune checkpoint therapy.
Epidemiology, Etiology and Clinical Aspects of Childhood Acute Encephalitis in a Tertiary Pediatric Hospital in Costa Rica.

BACKGROUND Limited data are available on childhood encephalitis in Latin America. Our study aimed to increase insight on clinical presentation, etiology and outcome of children with acute encephalitis in Costa Rica. METHODS We conducted a prospective, observational study during an 8-month period at the Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera" in Costa Rica. Case definition was according to "International Encephalitis Consortium" in children <13 years. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. RESULTS Forty patients were identified. Mean age was 5 years and 57.5% were male. Most frequently neurologic symptoms were altered mental status (100.0%), headache (57.5%) and seizures (52.5%). Etiology was determined in 52.5% of cases. Probable or confirmed viral etiology was identified in 6 cases (15.0%) and bacterial etiology in also 6 cases (15.0%). A possible etiology was identified in 7 cases (17.5%). Autoimmune encephalitis was diagnosed in 2 patients (5.0%). Enterovirus and Streptococcus pneumoniae were the most common confirmed agents. No cases of herpes simplex virus were found. Etiology of 19 cases (47.5%) remained unknown. Sequelae were reported in 45.0% of patients. Mortality rate was 15.0% (6 cases), 3 caused by virus (adenovirus, human herpesvirus 6, enterovirus), 2 by bacteria (S. pneumoniae, Haemophilus influenzae type b) and 1 of unknown etiology. Diffuse cerebral edema was the most important mortality predictor (P < 0.001). CONCLUSIONS Acute encephalitis in our study was associated with significant morbidity and mortality. Early and aggressive antiviral, antibiotic and anticerebral edema treatment is necessary when acute encephalitis is suspected.
The influence of rewards on incidental memory: more does not mean better

Studies have revealed that rewards promote long-term memory, even in an incidental way. However, most previous studies using the incidental paradigm have included two reward levels, and it is still not clear how the reward magnitude influences memory. Adopting the incidental paradigm and three reward levels, the current study revealed that the reward magnitude impacted 1-d delayed episodic memory in a nonlinear, inverted U-shaped pattern. An additional experiment showed that there was no reward effect in immediate episodic memory. Our results support the dopaminergic memory consolidation theory and further imply that the reward magnitude needs to be considered in the theory.
Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the miR-149/let-7c/Faslg axis

Abstract Ischaemia-reperfusion injury (IRI) is closely related to cardiovascular disease (CVD), which is the leading cause of death and disability. Exosomes appear to be involved in several diseases, including CVD. However, the role of mesenchymal stem cell (MSC)-derived exosomes in IRI remains unclear. miRNA expression levels in exosomes from rat normal MSCs or hypoxia-reoxygenation (H/R) MSCs were determined by qPCR and the two significantly upregulated miRNAs were selected for further investigation. Rat cardiomyoblasts (H9c2) were transfected with either miRNA mimics or scramble controls, followed by H/R induction. The effects of miRNA overexpression and exosome administration on H/R damage were then investigated. H/R increased Faslg, suppressed β-catenin, inhibited cell proliferation and migration, and stimulated apoptosis and reactive oxygen species (ROS) production. miR-149 or Let-7c mimics or exosomes reversed H/R-induced damage. The luciferase reporter assay proved the targeted regulation of Faslg by both miR149 and Let-7c. Inhibition of β-catenin suppressed cell migration, proliferation, and ΔΨm but increased apoptosis and ROS. Overall, bone marrow MSC-derived exosomes protected rat cardiomyoblasts from H/R injury via the miR-149/Let-7c/Faslg axis.
No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine

Introduction Despite recent advances in migraine treatment there is a need for therapies with higher clinical efficacy and/or fewer side effects. Triptans (5-HT1B/1D/1F agonists) are essential in the present treatment regime and gepants (CGRP-receptor antagonists) are recognized as effective in acute migraine treatment. Triptans and gepants have different mechanisms of action and here we tested the hypothesis that a combination of these drugs (sumatriptan and olcegepant) would result in an additive effect. Methods Using the validated glyceryl trinitrate mouse model of migraine, we initially tested dose-response relationships of sumatriptan (0.1, 0.3, and 0.6 mg/kg IP) and olcegepant (0.25, 0.50, and 1.0 mg/kg IP) to find suitable high and low doses. Subsequently, we performed a combination study of the two drugs with a low and a high dose. All experiments were vehicle (placebo) controlled and blinded. Results Sumatriptan significantly reduced glyceryl trinitrate-induced allodynia (F(4,54) = 13.51, p < 0.0001) at all doses. Olcegepant also reduced glyceryl trinitrate-induced allodynia (F(4,53) = 16.11, p < 0.0001) with the two higher doses being significantly effective. Combining 0.50 mg/kg olcegepant with 0.1 or 0.6 mg/kg sumatriptan did not have any improved effect compared to either drug alone (p > 0.50 on all days) in our mouse model. Conclusion Combining olcegepant and sumatriptan did not have an additive effect compared to single-drug treatment in this study. Triptan-gepant combinations will therefore most likely not improve migraine treatment. Nevertheless, further studies are necessary, and combinations should also be examined in patients with migraine.
Evaluation of undergraduate Endodontic teaching in dental schools within Spain.

AIM To evaluate the current situation of undergraduate endodontic teaching in Spanish dental schools. METHODOLOGY An online version, translated into Spanish, of a survey conducted in the UK (Al Raisi et al. 2019) was sent via email to the undergraduate endodontic program leads in the 23 Spanish dental schools. RESULTS The response rate was 96%. In 95% of dental schools endodontics is taught in the fourth year. Students treat simple root canal treatment cases in 100% of schools and only in 40% treat moderate cases. In 65% of schools students are supervised by full-time professors who are specialists in Endodontics, significantly more frequently in private dental schools (p = 0.002). Spanish dental schools use both rotary and reciprocating instrumentation systems during endodontic training, with consistency on methods of working length determination, use of silicate-based endodontic cements, irrigating solutions, inter-visit medicaments and canal filling techniques. No type of magnification is used in 90% of dental schools and only 25% use ultrasonic instruments. Private dental schools have a significantly better staff: student ratio during clinical practice (p = 0.041), spend significantly more hours in clinical training (p = 0.04), and have significantly greater number of areas specifically dedicated to Endodontics (p = 0.010). CONCLUSIONS Undergraduate endodontic teaching in Spanish dental schools follows the key recommendations of the ESE Undergraduate Curriculum Guidelines (ESE 2013), being, in most respects, comparable to that carried out in the UK (Al Raisi et al. 2019). The use of magnification and ultrasonic instruments need to be increased. Private schools reported better results than public schools in some of the analysed variables.
Nasopharyngeal Microbiota Analysis in Healthy and Otitis-prone Children

Background: Recurrent acute otitis media (RAOM) is common in children, and it may result in spontaneous tympanic membrane perforation (STMP), management of which is often challenging. In the upper respiratory tract (URT), resident microorganisms play a pivotal role in otitis media pathogenesis and prevention, as they are able to inhibit the colonization process and otopathogens growth. In particular, Dolosigranulum spp. and Corynebacterium spp. have been associated with respiratory health in several studies. This study aims at comparing both nasopharyngeal microbiota of children with RAOM versus matched controls and nasopharyngeal microbiota of children with a history of RAOM with STMP. Method: Nasopharyngeal swabs were collected from 132 children, median age 3.51 (2.13–4.72), including 36 healthy children, 50 with RAOM without STMP, and 46 with RAOM with STMP. Bacterial DNA was subsequently extracted and 16S rRNA gene V3-V4 regions were polymerase chain reaction amplified and sequenced using Illumina MiSeq technology. Results: A higher relative abundance of Dolosigranulum and Corynebacterium genera was detected in the nasopharynx of healthy children (16.5% and 9.3%, respectively) in comparison with RAOM without STMP (8.9% and 4.3%, respectively) and RAOM with STMP (5.2% and 2.8%, respectively). A decreasing pattern in relative abundance of these 2 pivotal genera through disease severity was detected. In all groups, the most abundant genera were Moraxella, Streptococcus and Haemophilus, followed by Dolosigranulum and Corynebacterium. Conclusions: Our study provides a characterization of the URT microbiota in otitis-prone children with and without history of recurrent STMP, suggesting that the role of Dolosigranulum and Corynebacterium in regulating the healthy URT microbiota should be further studied.
Regulation of DNA Replication Initiation by Histone Acetylation and the DNA Unwinding Element Binding Protein DUE-B

Kemp, Michael G. Ph.D., Biomedical Sciences Program, Wright State University, 2006. Regulation of DNA Replication Initiation by Histone Acetylation and the DNA Unwinding Element Binding Protein DUE-B. Duplication of the genome during S phase of the mitotic cell cycle begins at thousands of sites along chromosomes termed origins of replication. Although many of the essential protein components catalyzing events at these sites are known and are conserved throughout eukaryotes, the likelihood or efficiency of initiation of DNA synthesis at any given genomic site is expected to be influenced by other novel factors, including aspects of chromatin and DNA structure. Here I show that increased histone H4 acetylation at replication origin loci occurs after treatment with the histone deacetylase inhibitor TSA and coincides with a loss of specific initiation site selection both within origin loci and throughout the genome. Furthermore, new replication initiation sites become activated or used with greater frequency after treatment with TSA, and TSA promotes the activation of replication origins earlier during the S phase of the cell cycle. These data suggest a physiological role for histone acetylation in controlling the initiation of DNA synthesis at specific
Analysis of 16S rRNA genes reveals reduced Fusobacterial community diversity when translocating from saliva to GI sites

ABSTRACT Fusobacterium nucleatum is a Gram-negative oral commensal anaerobe which has been increasingly implicated in various gastrointestinal (GI) disorders, including inflammatory bowel disease, appendicitis, GI cancers. The oral cavity harbors a diverse group of Fusobacterium, and it is postulated that F. nucleatum in the GI tract originate from the mouth. It is not known, however, if all oral Fusobacterium translocate to the GI sites with equal efficiencies. Therefore, we amplified 16S rRNA genes of F. nucleatum and F. periodonticum, two closely related oral species from matched saliva, gastric aspirates, and colon or ileal pouch aspirates of three patients with inflammatory bowel disease (IBD) and three healthy controls, and saliva alone from seven patients with either active IBD or IBD in remission. The 16S rRNA gene amplicons were cloned, and the DNA sequences determined by Sanger sequencing. The results demonstrate that fusobacterial community composition differs more significantly between the oral and GI sites than between different individuals. The oral communities demonstrate the highest level of variation and have the richest pool of unique sequences, with certain nodes/strains enriched in the GI tract and others diminished during translocation. The gastric and colon/pouch communities exhibit reduced diversity and are more closely related, possibly due to selective pressure in the GI tract. This study elucidates selective translocation of oral fusobacteria to the GI tract. Identification of specific transmissible clones will facilitate risk assessment for developing Fusobacterium-implicated GI disorders.