Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Lower Third Molar Segmentations on Automated Tooth Development Staging using a Convolutional Neural Network

Staging third molar development is commonly used for age estimation in subadults. Automated developmental stage allocation to the mandibular left third molar in panoramic radiographs has been examined in a pilot study. This method used an AlexNet Deep Convolutional Neural Network (CNN) approach to stage lower left third molars, which had been selected by manually drawn bounding boxes around them. This method (bounding box AlexNet = BA) still contained parts of surrounding structures which may have affected the automated stage allocation performance. We hypothesize that segmenting only the third molar could further improve the automated stage allocation performance. Therefore, the current study aimed to determine and validate the effect of lower third molar segmentations on automated tooth development staging. Retrospectively, 400 panoramic radiographs were collected, processed and segmented in three ways: bounding box (BB), rough (RS), and full (FS) tooth segmentation. A DenseNet201 CNN was used for automated stage allocation. Automated staging results were compared with reference stages – allocated by human observers – overall and per stage. FS rendered the best results with a stage allocation accuracy of 0.61, a mean absolute difference of 0.53 stages and a Cohen's linear κ of 0.84. Misallocated stages were mostly neighboring stages, and DenseNet201 rendered better results than AlexNet by increasing the percentage of correctly allocated stages by 3% (BA compared to BB). FS increased the percentage of correctly allocated stages by 7% compared to BB. In conclusion, full tooth segmentation and a DenseNet CNN optimize automated dental stage allocation for age estimation.
Does Juvenile Play Programme the Equine Musculoskeletal System?

Simple Summary Locomotor play is a common behaviour expressed across a diverse range of species. As a cursorial animal, the horse is capable of locomotor activity within a relatively short time after birth. In the foal, spontaneous locomotor play occurs early in life and has an obvious role in the development of locomotor skills. The intensity and vigour of locomotor play increases with age and this, in turn, provides cumulative increases in the loads the musculoskeletal system experiences. These progressive cumulative loading cycles (bouts of locomotor play), in both the timing and magnitude, reflect the microstrain required to stimulate bone development based on the mechanostat theorem. Data from the published literature were presented to provide empirical support for this hypothesis. Thus, spontaneous locomotor play may be vital to ensure optimal bone development in the horse. Modern production systems need to provide appropriate opportunities for foals to perform spontaneous locomotor play to optimise bone development and reduce the risk of future musculoskeletal injury later in life. Abstract In mammals, play behaviour appears innate and, because of this, may provide insight into the frequency and intensity of load that is required to stimulate positive musculoskeletal development. The objective of this review was to explore the interaction between play and tissue (bone) development at a molecular through to whole-animal level, with specific focus on the horse as a model. The basis of our understanding of the response of bone to loading is the mechanostat theorem. This assumes that at a tissue level, bone attempts to keep localised strain within the physiological range of 1500–2500 microstrain. Loads above this range result in a modelling response to reduce strain, and strain below this threshold results in remodelling to maintain the localised physiological range. In foals, locomotor play is dramatic and vigorous, with cumulative increases in both intensity and complexity. Based on published literature describing locomotor play in foals and the microstrain at different gaits in the horse, it was proposed that locomotor play in foal aligns with the mechanostat theorem in both the magnitude and frequency of load cycles applied. The cumulative increases in the complexity and intensity of locomotor play as the foal develops, in turn, ensure the strain rates associated with play remain above the local physiological range and promote material and architectural changes in the distal limb bones. Thus, spontaneous locomotor play may be vital to ensure optimal bone development in the horse. Modern management systems need to provide appropriate opportunities for foals to perform spontaneous locomotor play to optimise bone development and reduce the risk of future musculoskeletal injury later in life.
Modulating Mistranslation Potential of tRNASer in Saccharomyces cerevisiae

Mistranslation, incorporating an amino acid not specified by the “standard” genetic code, has applications in research and synthetic biology. Since mistranslation is toxic, its level must be modulated. Using a serine tRNA with a proline anticodon, we identify. Transfer RNAs (tRNAs) read the genetic code, translating nucleic acid sequence into protein. For tRNASer the anticodon does not specify its aminoacylation. For this reason, mutations in the tRNASer anticodon can result in amino acid substitutions, a process called mistranslation. Previously, we found that tRNASer with a proline anticodon was lethal to cells. However, by incorporating secondary mutations into the tRNA, mistranslation was dampened to a nonlethal level. The goal of this work was to identify second-site substitutions in tRNASer that modulate mistranslation to different levels. Targeted changes to putative identity elements led to total loss of tRNA function or significantly impaired cell growth. However, through genetic selection, we identified 22 substitutions that allow nontoxic mistranslation. These secondary mutations are primarily in single-stranded regions or substitute G:U base pairs for Watson–Crick pairs. Many of the variants are more toxic at low temperature and upon impairing the rapid tRNA decay pathway. We suggest that the majority of the secondary mutations affect the stability of the tRNA in cells. The temperature sensitivity of the tRNAs allows conditional mistranslation. Proteomic analysis demonstrated that tRNASer variants mistranslate to different extents with diminished growth correlating with increased mistranslation. When combined with a secondary mutation, other anticodon substitutions allow serine mistranslation at additional nonserine codons. These mistranslating tRNAs have applications in synthetic biology, by creating “statistical proteins,” which may display a wider range of activities or substrate specificities than the homogenous form.
Development of a Biomimetic Extensor Mechanism for Restoring Normal Kinematics of Finger Movements Post-Stroke

Cable-driven devices for hands allow compact and lightweight design that could provide various functional movements. However, for many patients post-stroke, cable-driven devices produce nonphysiologic movements, such as metacarpophalangeal joint hyperextension, due to their abnormal passive joint impedance. In this study, we developed a novel bio-inspired device mimicking the anatomy of the extensor mechanism of the human finger, which can be tuned for individuals to provide ‘subject-specific’ assistance to achieve physiological movement patterns. We first evaluated the proposed design via mathematical modeling and computer simulation. Its performance was then tested experimentally with twenty-four subjects, including six healthy and eighteen chronic stroke survivors. We determined the loading condition of the device from the experimental identification of passive joint impedance of each subject before device use. Our results showed that the proposed design could achieve improved spatiotemporal coordination of finger movements compared to conventional cable-driven design by providing ‘subject-specific’ assistance based on identified passive stiffness values of each subject. We also identified a significant (negative) correlation between the metacarpophalangeal joint stiffness and the intrinsic exotendon loading level across subjects. The proposed system can restore normal movement patterns for patients with different types of impairments, which were previously found important in improving rehabilitative outcomes.
Pregnancy Outcomes After Human Papillomavirus Vaccination in Periconceptional Period or During Pregnancy: A Systematic Review and Meta-analysis

ABSTRACT Background: National immunization schedules in many countries recommend HPV vaccination for females until the age of 26 years, and thus substantial numbers with reproductive age may be exposed to HPV vaccines. Objective: To assess whether inadvertent HPV vaccine exposures in the periconceptional period or during pregnancy were associated with increased risks for adverse pregnancy outcomes. Search strategy: A search of PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang databases (until March 31, 2019) was performed. Selection criteria: Studies that assess the risk of adverse pregnancy outcomes in HPV vaccine exposed/unexposed pregnancies were included. The adverse pregnancy outcomes included spontaneous abortion, stillbirth, small for sestational age, preterm birth, and birth defects. Data collection and analysis: The pooled relative risk (RR) was applied for the effect measure of the study. RRs and 95% confidence interval (CI) were measured when the paper did not report the effect. Heterogeneity between studies was assessed using the Cochrane’s Q and I2 statistics. Main results: Of 374 identified citations, 8 met inclusion criteria. Compared with the unexposed pregnancies, HPV vaccine exposed pregnancies were associated with no higher risk for spontaneous abortion (RR, 0.99 [95% CI, 0.90 to 1.08]); stillbirth (RR, 1.16 [95% CI, 0.71 to 1.90]); small for gestational age (RR, 0.96 [95% CI, 0.86 to 1.07]); preterm birth (RR, 1.04 [95% CI, 0.91 to 1.18]); or birth defects (RR, 1.18 [95% CI, 0.97 to 1.43]). Conclusions: Inadvertent bivalent/quadrivalent HPV vaccination during pregnancy was not associated with significantly greater risks of adverse pregnancy outcomes.
The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell–specific adapter protein

T-cell activation requires stimulation of specific intracellular signaling pathways in which protein-tyrosine kinases, phosphatases, and adapter proteins interact to transmit signals from the T-cell receptor to the nucleus. Interactions of LCK proto-oncogene, SRC family tyrosine kinase (LCK), and the IL-2–inducible T cell kinase (ITK) with the T cell-specific adapter protein (TSAD) promotes LCK-mediated phosphorylation and thereby ITK activation. Both ITK and LCK interact with TSAD's proline-rich region (PRR) through their Src homology 3 (SH3) domains. Whereas LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3 domain. To begin to understand on a molecular level how the LCK SH3 and ITK SH3 domains interact with TSAD in human HEK293T cells, here we combined biochemical analyses with NMR spectroscopy. We found that the ITK and LCK SH3 domains potentially have adjacent and overlapping binding sites within the TSAD PRR amino acids (aa) 239–274. Pulldown experiments and NMR spectroscopy revealed that both domains may bind to TSAD aa 239–256 and aa 257–274. Co-immunoprecipitation experiments further revealed that both domains may also bind simultaneously to TSAD aa 242–268. Accordingly, NMR spectroscopy indicated that the SH3 domains may compete for these two adjacent binding sites. We propose that once the associations of ITK and LCK with TSAD promote the ITK and LCK interaction, the interactions among TSAD, ITK, and LCK are dynamically altered by ITK phosphorylation status.
Genotyping‐in‐Thousands by sequencing (GT‐seq) panel development and application to minimally invasive DNA samples to support studies in molecular ecology

Minimally invasive sampling (MIS) is widespread in wildlife studies; however, its utility for massively parallel DNA sequencing (MPS) is limited. Poor sample quality and contamination by exogenous DNA can make MIS challenging to use with modern genotyping‐by‐sequencing approaches, which have been traditionally developed for high‐quality DNA sources. Given that MIS is often more appropriate in many contexts, there is a need to make such samples practical for harnessing MPS. Here, we test the ability for Genotyping‐in‐Thousands by sequencing (GT‐seq), a multiplex amplicon sequencing approach, to effectively genotype minimally invasive cloacal DNA samples collected from the Western Rattlesnake (Crotalus oreganus), a threatened species in British Columbia, Canada. As there was no previous genetic information for this species, an optimized panel of 362 SNPs was selected for use with GT‐seq from a de novo restriction site‐associated DNA sequencing (RADseq) assembly. Comparisons of genotypes generated within and among RADseq and GT‐seq for the same individuals found low rates of genotyping error (GT‐seq: 0.50%; RADseq: 0.80%) and discordance (2.57%), the latter likely due to the different genotype calling models employed. GT‐seq mean genotype discordance between blood and cloacal swab samples collected from the same individuals was also minimal (1.37%). Estimates of population diversity parameters were similar across GT‐seq and RADseq data sets, as were inferred patterns of population structure. Overall, GT‐seq can be effectively applied to low‐quality DNA samples, minimizing the inefficiencies presented by exogenous DNA typically found in minimally invasive samples and continuing the expansion of molecular ecology and conservation genetics in the genomics era.
Tracking Electromechanical Systems Design with Sensorless Manipulators

For an all-wheel drive electromechanical system, a discontinuous control law has been developed within the framework of the block approach. It provides tracking of given signals of generalized coordinates and invariance with respect to external and parametric disturbances. For the case when the sensors are located only on the drives, a dual-circuit information system is design. It includes two observers with piecewise linear corrective actions for estimating generalized coordinates and mixed variables necessary for feedback design.
A Review of Dietary (Phyto)Nutrients for Glutathione Support

Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.
Clofarabine-phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase-dependent apoptosis

Clofarabine (2-chloro-2′-fluoro-2′-deoxyarabinosyladenine, CIF), a second-generation 2′-deoxyadenosine analog, possesses a variety of anti-cancer activities, including the capacity to modulate DNA methylation marks. Bioactive nutrients, including resveratrol (RSV) and all-trans retinoic acid (ATRA) have been indicated to regulate epigenetic machinery in malignant cells. The purpose of the current study was to evaluate whether the tested phytochemicals, RSV or ATRA, can improve the therapeutic epigenetic effects of CIF in chronic myeloid leukemia (CML) cells. The present study investigates, to the best of our knowledge, for the first time, the influence of CIF in combination with RSV or ATRA on the expression of relevant modifiers of DNA methylation machinery, including DNA Methyltransferase 1 (DNMT1) and Cyclin dependent kinase inhibitor 1A (CDKN1A) in CML cells. Subsequently, the combinatorial effects on promoter methylation and transcript levels of methylation-silenced tumor suppressor genes (TSGs), including phosphatase and tensin homologue (PTEN) and retinoic acid receptor beta (RARB), were estimated using MSRA and qPCR, respectively. The tested TSGs were chosen according to bioinformatical analysis of publicly available clinical data of human DNA methylation and gene expression arrays in leukemia patients. The K562 cell line was used as an experimental CML in vitro model. Following a period of 72 h exposure of K562 cells, the tested combinations led to significant cell growth inhibition and induction of caspase-3-dependent apoptosis. These observations were accompanied by DNMT1 downregulation and CDKN1A upregulation, with a concomitant enhanced decrease in DNMT1 protein level, especially after ATRA treatment with CIF. Concurrent methylation-mediated RARB and PTEN reactivation was detected. The results of the current study demonstrated that CIF that was used in combination with the tested phytochemicals, RSV or ATRA, exhibited a greater ability to remodel DNA methylation marks and promote cell death in CML cells. These results may support the application of CIF combinations with natural bioactive agents in anti-leukemic epigenetic therapy.
REV7 has a dynamic adaptor region to accommodate small GTPase RAN/Shigella IpaB ligands, and its activity is regulated by the RanGTP/GDP switch

REV7, also termed mitotic arrest–deficient 2-like 2 (MAD2L2 or MAD2B), acts as an interaction module in a broad array of cellular pathways, including translesion DNA synthesis, cell cycle control, and nonhomologous end joining. Numerous REV7 binding partners have been identified, including the human small GTPase Ras-associated nuclear protein (RAN), which acts as a potential upstream regulator of REV7. Notably, the Shigella invasin IpaB hijacks REV7 to disrupt cell cycle control to prevent intestinal epithelial cell renewal and facilitate bacterial colonization. However, the structural details of the REV7–RAN and REV7–IpaB interactions are mostly unknown. Here, using fusion protein and rigid maltose-binding protein tagging strategies, we determined the crystal structures of these two complexes at 2.00–2.35 Å resolutions. The structures revealed that both RAN and IpaB fragments bind the “safety belt” region of REV7, inducing rearrangement of the C-terminal β-sheet region of REV7, conserved among REV7-related complexes. Of note, the REV7-binding motifs of RAN and IpaB each displayed some unique interactions with REV7 despite sharing consensus residues. Structural alignments revealed that REV7 has an adaptor region within the safety belt region that can rearrange secondary structures to fit a variety of different ligands. Our structural and biochemical results further indicated that REV7 preferentially binds GTP-bound RAN, implying that a GTP/GDP-bound transition of RAN may serve as the molecular switch that controls REV7's activity. These results provide insights into the regulatory mechanism of REV7 in cell cycle control, which may help with the development of small-molecule inhibitors that target REV7 activity.
Reference Trajectory Reshaping Optimization and Control of Robotic Exoskeletons for Human–Robot Co-Manipulation

For human–robot co-manipulation by robotic exoskeletons, the interaction forces provide a communication channel through which the human and the robot can coordinate their actions. In this article, an optimization approach for reshaping the physical interactive trajectory is presented in the co-manipulation tasks, which combines impedance control to enable the human to adjust both the desired and the actual trajectories of the robot. Different from previous studies, the proposed method significantly reshapes the desired trajectory during physical human–robot interaction (pHRI) based on force feedback, without requiring constant human guidance. The proposed scheme first formulates a quadratically constrained programming problem, which is then solved by neural dynamics optimization to obtain a smooth and minimal-energy trajectory similar to the natural human movement. Then, we propose an adaptive neural-network controller based on the barrier Lyapunov function (BLF), which enables the robot to handle the uncertain dynamics and the joint space constraints directly. To validate the proposed method, we perform experiments on the exoskeleton robot with human operators for co-manipulation tasks. The experimental results demonstrate that the proposed controller could complete the co-manipulation tasks effectively.
The mental health needs and concerns of older people who identify as LGBTQ+: A narrative review of the international evidence.

AIMS To synthesize the best available evidence on the experiences and perceptions of older people who identify as LGBTQ+ regarding their mental health needs and concerns. DESIGN A narrative review and critical appraisal of qualitative, quantitative and mixed methods studies. DATA SOURCES A systematic search was undertaken across all of the databases including PsycINFO, MEDLINE, CINAHL and Sociological Abstracts. International studies published in academic journals in the English language, from January 1995 to January 2019 were appraised. Studies had to involve older people identifying as LGBTQ+ and who had experiences mental health issues. REVIEW METHODS Fourteen papers were selected for inclusion in the systematic review. A narrative analysis of the papers was used by synthesizing the key findings and organizing them into themes and concepts. RESULTS Following analysis of the data, the themes that emerged were: (i) LGBTQ+ identity issues (ii) risk and vulnerability factors, (iii) coping strategies and resilience, (iv) interventions and supports. CONCLUSION This review highlights key mental health-related issues that need to be taken into account in the creation and provision of appropriate, responsive and inclusive supports and services. This article is protected by copyright. All rights reserved.