Convolutional neural networks combined with classification algorithms for the diagnosis of periodontitis.

OBJECTIVES: We aim to develop a deep learning model based on a convolutional neural network (CNN) combined with a classification algorithm (CA) to assist dentists in quickly and accurately diagnosing the stage of periodontitis. MATERIALS AND METHODS: Periapical radiographs (PERs) and clinical data were collected. The CNNs including Alexnet, VGG16, and ResNet18 were trained on PER to establish the PER-CNN models for no periodontal bone loss (PBL) and PBL. The CAs including random forest (RF), support vector machine (SVM), naive Bayes (NB), logistic regression (LR), and k-nearest neighbor (KNN) were added to the PER-CNN model for control, stage I, stage II and stage III/IV periodontitis. Heat map was produced using a gradient-weighted class activation mapping method to visualize the regions of interest of the PER-Alexnet model. Clustering analysis was performed based on the ten PER-CNN scores and the clinical characteristics. RESULTS: The accuracy of the PER-Alexnet and PER-VGG16 models with the higher performance was 0.872 and 0.853, respectively. The accuracy of the PER-Alexnet + RF model with the highest performance for control, stage I, stage II and stage III/IV was 0.968, 0.960, 0.835 and 0.842, respectively. Heat map showed that the regions of interest predicted by the model were periodontitis bone lesions. We found that age and smoking were significantly related to periodontitis based on the PER-Alexnet scores. CONCLUSION: The PER-Alexnet + RF model has reached high performance for whole-case periodontal diagnosis. The CNN models combined with CA can assist dentists in quickly and accurately diagnosing the stage of periodontitis.

Persistent Targeting DNA Nanocarrier Made of 3D Structural Unit Assembled from Only One Basic Multi-Palindromic Oligonucleotide for Precise Gene Cancer Therapy.

Construction of a simple, reconfigurable, and stimuli-responsive DNA nanocarrier remains a technical challenge. In this contribution, by designing three palindromic fragments, a simplest four-sticky end-contained 3D structural unit (PS-unit) made of two same DNA components is proposed. Via regulating the rotation angle of central longitudinal axis of PS-unit, the oriented assembly of one-component spherical architecture is accomplished with high efficiency. Introduction of an aptamer and sticky tail warehouse into one component creates a size-change-reversible targeted siRNA delivery nanovehicle. Volume swelling of 20 nm allows one carrier to load 1987 siPLK1s. Once entering cancer cells and responding to glutathione (GSH) stimuli, siPLK1s are almost 100% released and original size of nanovehicle is restored, inhibiting the expression of PLK1 protein and substantially suppressing tumor growth (superior to commercial transfection agents) in tumor-bearing mice without systemic toxicity.

Multimodal prerehabilitation for elderly patients with sarcopenia in colorectal surgery.

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.

Transanal Total Mesorectal Excision With Delayed Coloanal Anastomosis (TaTME-DCAA) Versus Laparoscopic Total Mesorectal Excision (LTME) and Robotic Total Mesorectal Excision (RTME) for Low Rectal Cancer: A Propensity Score-Matched Analysis of Short-term Outcomes, Bowel Function, and Cost.

INTRODUCTION: Total mesorectal excision (TME) with delayed coloanal anastomosis (DCAA) is surgical option for low rectal cancer, replacing conventional immediate coloanal anastomosis (ICAA) with bowel diversion. This study aimed to assess the outcomes of transanal TME (TaTME) with DCAA versus laparoscopic TME (LTME) with ICAA versus robotic TME (RTME) with ICAA. METHODS: This was a retrospective propensity score-matched analysis of patients who underwent elective TaTME-DCAA between November 2021 and June 2022. Patients were propensity-score matched in a ratio of 1:3 to patients who underwent LTME-ICAA and RTME-ICAA from January 2019 to December 2020. Outcome measures were histopathologic results, postoperative morbidity, function, and inpatient costs. RESULTS: Twelve patients in the TaTME-DCAA group were compared with 36 patients in the LTME-ICAA and RTME-ICAA groups each after propensity score matching. Histopathologic results and postoperative morbidity rates were statistically similar. Overall stoma-related complication rates in the ICAA groups were 11%. Median total length of hospital stays for TME plus stoma reversal surgery was similar across all techniques (10 vs. 10 vs. 9 days; P =0.532). Despite a significantly shorter duration of follow-up, bowel function after TaTME-DCAA was comparable to that of LTME-ICAA and RTME-ICAA. Overall median inpatient costs of TaTME-DCAA were comparable to LTME-ICAA and significantly cheaper than RTME-ICAA ($31,087 vs. $29,927 vs. $36,750; P =0.002). CONCLUSIONS: TaTME with DCAA is a feasible and safe technique compared with other minimally invasive methods of TME, while avoiding bowel diversion and stoma-related complications, as well as comparing favorably in terms of overall hospitalization costs.

Cryo-EM structure of the fatty acid reductase LuxC-LuxE complex provides insights into bacterial bioluminescence.

The discovery of reduced flavin mononucleotide and fatty aldehydes as essential factors of light emission facilitated study of bacterial luminescence. Although the molecular mechanisms underlying bacterial luminescence have been studied for more than 60 years, the structure of the bacterial fatty acid reductase complex remains unclear. Here, we report the cryo-EM structure of the Photobacterium phosphoreum fatty acid reductase complex LuxC-LuxE to a resolution of 2.79 Å. We show that the active site Lys238/Arg355 pair of LuxE is >30 Å from the active site Cys296 of LuxC, implying that catalysis relies on a large conformational change. Furthermore, mutagenesis and biochemical experiments support that the L-shaped cleft inside LuxC plays an important role in substrate binding and reaction. We obtained a series of mutants with significantly improved activity as measured by in vitro bioluminescence assays and demonstrated that the double mutant W111A/F483K displayed the highest activity (370% of the WT). Our results indicated that the activity of LuxC significantly affects the bacterial bioluminescence reaction. Finally, we expressed this mutated lux operon in Escherichia coli but observed that the in vivo concentrations of ATP and NADPH limited the enzyme activity; thus, we conclude that the luminous intensity mainly depends on the level of metabolic energy.

Hybridization chain reaction and its applications in biosensing.

To pursue the sensitive and efficient detection of informative biomolecules for bioanalysis and disease diagnosis, a series of signal amplification techniques have been put forward. Among them, hybridization chain reaction (HCR) is an isothermal and enzyme-free process where the cascade reaction of hybridization events is initiated by a target analyte, yielding a long nicked dsDNA molecule analogous to alternating copolymers. Compared with conventional polymerase chain reaction (PCR) that can proceed only with the aid of polymerases and complicated thermal cycling, HCR has attracted increasing attention because it can occur under mild conditions without using enzymes. As a powerful signal amplification tool, HCR has been employed to construct various simple, sensitive and economic biosensors for detecting nucleic acids, small molecules, cells, and proteins. Moreover, HCR has also been applied to assemble complex nanostructures, some of which even act as the carriers to execute the targeted delivery of anticancer drugs. Recently, HCR has engendered tremendous progress in RNA imaging applications, which can not only achieve endogenous RNA imaging in living cells or even living animals but also implement imaging-guided photodynamic therapy, paving a promising path to promote the development of theranostics. In this review, we begin with the fundamentals of HCR and then focus on summarizing the recent advances in HCR-based biosensors for biosensing and RNA imaging strategies. Further, the challenges and future perspective of HCR-based signal amplification in biosensing and theranostic application are discussed.

Editor's Choice - Decrease in Mortality from Abdominal Aortic Aneurysms (2001 to 2015): Is it Decreasing Even Faster?

OBJECTIVE: The early twenty first century witnessed a decrease in mortality from abdominal aortic aneurysms (AAA), which was associated with variations in the prevalence of cardiovascular risk factors. This study investigated whether these trends continued into the second decade of the twenty first century. METHODS: Information on AAA mortality (2001 - 2015) using International Classification of Diseases codes was extracted from the World Health Organization (WHO) mortality database. Data on risk factors were extracted from the Institute of Health Metrics and Evaluation and WHO InfoBase, and data on population from the World Development Indicators database. Regression analysis of temporal trends in cardiovascular risk factors was done independently for correlations with AAA mortality trends. RESULTS: Seventeen countries across four continents met the inclusion criteria (Australasia, two; Europe, 11; North America, two; Asia, two). Male AAA mortality decreased in 13 countries (population weighted average: -2.84%), while female AAA mortality decreased in 11 countries (population weighted average: -1.64%). The decrease in AAA mortality was seen in both younger (< 65 years) and older (> 65 years) patients. The decrease in AAA mortality was more marked in the second decade of the twenty first century (2011 - 2015) compared with the first decade (2001 - 2005 and 2006 - 2010). Trends in AAA mortality positively correlated with smoking (males: p = .03X, females: p = .001) and hypertension (males: p = .001, females: p = .01X). Conversely, AAA mortality negatively correlated with obesity (males: p = .001, females: p = .001), while there was no significant correlation with diabetes. CONCLUSION: AAA mortality has continued to decline and seems to have declined at an even faster rate in the second decade of the twenty first century, albeit with heterogeneity among countries. These variations are multifactorial in origin but further efforts targeting smoking cessation and blood pressure control will probably contribute to continued reductions in AAA mortality.

The hierarchical assembly of a multi-level DNA ring-based nanostructure in a precise order and its application for screening tumor cells.

DNA nanotechnology can be used to precisely construct nanostructures of different shapes, sizes and surface chemistry, which is appreciated in a variety of areas such as biomaterials, nanodevices, disease diagnosis, imaging, and drug delivery. Enzymatic degradation resistance and cell-targeting capability are indispensable for the applications of DNA nanostructures in biological and biomedical fields, and is challenging to rationally design the desirable nanoscale DNA materials suitable for the clinical translation by the existing assembly methodologies. Herein, we present a simple and efficient method for the hierarchical assembly of a three-level DNA ring-based nanostructure (DNA h-Nanoring) in a precise order, where DNA compositions at the primary level, the second level and the third level are a single DNA ring, two-ring-hybridized duplex and uniform complex macro-cycle, respectively. Most as-assembled DNA h-Nanorings exhibit the regular two-dimensional cycle-shaped structure characterized by atomic force microscopy (AFM). The Nanoring exhibits a significantly enhanced resistance to enzymatic attack, such that it can remain intact in 10% fetal bovine serum (FBS) for 24 h, and even stably exist in the presence of nuclease at a high concentration. More importantly, it is very easy to modify the DNA h-Nanoring with functional moieties (e.g., targeting ligand aptamer) because there are many single-stranded fragments available for further hybridization. By combining with receptor-targeted Sgc8, the nanoring can be used to accomplish the cell imaging and criminate target CEM cells from control cells, demonstrating a potential platform for in vivo tumor imaging and targeted chemotherapeutics delivery.

Tibiofemoral Contact Mechanics After Horizontal or Ripstop Suture in Inside-Out and Transtibial Repair for Meniscus Radial Tears in a Porcine Model.

PURPOSE: To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group. METHODS: Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments. RESULTS: All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P < .05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > .05). CONCLUSIONS: Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles. CLINICAL RELEVANCE: Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.

Results of a colorectal enhanced recovery after surgery (ERAS) programme and a qualitative analysis of healthcare workers' perspectives.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a structured programme using a multimodal, evidence-based approach to improve post-operative outcomes. Successful implementation of ERAS can be challenging. We aimed to evaluate our initial experience with colorectal ERAS and explore the perspectives of specialist doctors and nurses. METHODS: From 1 June 2017 to 31 December 2017, all patients who underwent elective colorectal resection and met the ERAS inclusion criteria at the Department of Colorectal Surgery, Singapore General Hospital, were included in the study. Short-term outcomes were compared between patients with >70% compliance to key ERAS components versus those with ≤70% compliance. Department staff were surveyed via questionnaire in July 2019. RESULTS: Three hundred and fifteen patients were included in study. >70% ERAS compliance rate was achieved in 84 patients (26.7%). A higher compliance rate resulted in a significantly shorter length of stay of 6 (IQR 5-8) days vs. 7 (IQR 6-9.5) days (p = 0.025) and lower readmission rate of 3.6% (n = 3) vs. 4.8% (n = 11) (p = 0.042), as well as a trend towards reduced complication rate of 15.4% (n = 13) vs. 22.0% (n = 51) and earlier return to gastrointestinal function. There was a 100% questionnaire response amongst all 12 colorectal surgeons and 5 colorectal resident nurse practitioners. CONCLUSION: Increased adherence to the components of ERAS results in better early outcomes and may have long-term benefits on survival. Effective communication and professional support for the ERAS multi-disciplinary team, as well as understanding healthcare workers' concerns and addressing long-standing practices, is essential for successful implementation of the programme.

Intracellular Nonenzymatic In Situ Growth of Three-Dimensional DNA Nanostructures for Imaging Specific Biomolecules in Living Cells.

Real-time in situ monitoring of low-abundance cancer biomarkers (e.g., miRNAs and proteins) in living cells by nonenzymatic assembly entirely from original DNA probes remains unexplored due to an extremely complex intracellular environment. Herein, a nonenzymatic palindrome-catalyzed DNA assembly (NEPA) technique is developed to execute the in situ imaging of intracellular miRNAs by assembling a three-dimensional nanoscale DNA spherical structure (NS) with low mobility from three free hairpin-type DNAs rather than from DNA intermediates based on the interaction of designed terminal palindromes. Target miRNA was detected down to 1.4 pM, and its family members were distinguished with almost 100% accuracy. The subcellular localization of NS products can be visualized in real time. The NEPA-based sensing strategy is also suitable for the intracellular in situ fluorescence imaging of cancer-related protein receptors, offering valuable insight into developing sensing protocols for understanding the biological function of vital biomolecules in disease pathogenesis and future therapeutic applications.

A coordinate-based meta-analysis of the n-back working memory paradigm using activation likelihood estimation.

The n-back task is a classical paradigm for functional neuroimaging studies of working memory (WM). The frontal and parietal cortical regions are known to be activated during the task. We used activation likelihood estimation (ALE) to conduct a quantitative meta-analysis of 96 primary studies of n-back task variants based on four conditions: memory loads (1-back, 2-back), object (identity, location), age (younger, older) and gender (male, female). Six cortical regions were consistently activated across all the studies: bilateral middle frontal gyrus (BA 10); bilateral inferior parietal lobule (BA 40); bilateral precuneus (BA 7); left superior frontal gyrus (BA 6); left anterior insula (aI) (BA 13); bilateral thalamus. Further meta-analyses revealed that different regions were sensitive to different conditions: compared with 1-back, 2-back increased activation in left middle frontal gyrus, left inferior frontal gyrus and left aI; compared with object location, object identity increased activation in right aI; young, compared with older subjects showed increased activation in frontal, parietal lobule, and right aI; the comparison between male and female showed no differences. Thus, our findings, showed consistent activation of frontal and parietal cortical regions, while other regions such as the aI, showed different activation patterns depending on varying experimental classification conditions.

Hole superiority effect with 3D figures formed by binocular disparity.

The global-first theory of topological perception claims that topological perception is prior to the perception of local features (e.g., Chen, 1982, 2005). Our previous studies demonstrated a hole superiority effect (HSE): Figures with holes are more detectable than figures without holes. Such an HSE was shown with figures formed by either orientation-defined texture (Zhang, 2009) or a black-and-white contrast (Meng, Cui, Zhou, Chen, & Ma, 2012). The present study used binocular disparity as one more organizing factor for testing the abstract nature of the HSE, indicating holes, as a typical kind of topological invariance, are represented in vision independent of the features that were forming the holes. The disparity-forming figures were well controlled for luminance, spatial frequency, subjective contours, and other nontopological factors, which are commonly considered as counter explanations against the topological theory.